Expression of Variant CD44 Messenger RNA in Colorectal Adenocarcinomas and Adenomatous Polyps in Humans

Save this PDF as:
 WORD  PNG  TXT  JPG

Size: px
Start display at page:

Download "Expression of Variant CD44 Messenger RNA in Colorectal Adenocarcinomas and Adenomatous Polyps in Humans"

Transcription

1 GASTROENTEROLOGY 1996;110: Expression of Variant CD44 Messenger RNA in Colorectal Adenocarcinomas and Adenomatous Polyps in Humans FUMIO IMAZEKI,* OSAMU YOKOSUKA,* TAKETO YAMAGUCHI,* MASAO OHTO,* KAICHI ISONO, and MASAO OMATA *First Department of Medicine and Second Department of Surgery, Chiba University School of Medicine, Chiba; and Second Department of Internal Medicine, Faculty of Medicine, Tokyo University, Tokyo, Japan C D44 molecule is a transmembrane glycoprotein expressed on a wide range of different cells and seems to have various functions such as a lymphocyte homing receptor on circulating lymphocytes 1 ; binding to collagen, fibronectin, and hyaluronate to confer cell-matrix contacts 2 4 ; and mediation of cell-cell adhesion. 5 CD44 molecules have heterogeneous isoforms, which are attributed both to variable exon usage with alternative splicing 4,6,7 and to differential glycosylation within the extracellular domain. Molecular cloning of CD44 disclosed the genomic region coding for exons 6 15, which are components of the extracellular domain of CD44 and can be incorporated alternatively into CD44 messenger RNA (mrna) (Figure 1). 8,9 Recent studies suggest that there are various isoforms of CD44 generated by this alternative splicing of exons 6 15 (variant exons Background & Aims: Recent studies have shown that some variant forms of CD44, a transmembrane glycoprotein expressed on various cell surfaces, might be involved in tumor progression or tumor metastasis. The aim of this study was to analyze the expression of CD44 messenger RNA (mrna) in colorectal cancer and colorectal adenoma to further elucidate the role of CD44 in colorectal tumorigenesis. Methods: The ex- pression of CD44-mRNA was examined in 90 specimens from 44 patients with colorectal cancer or colo- rectal adenomatous polyps and in the peripheral blood leukocytes from 7 healthy volunteers by reverse tran- scription polymerase chain reaction and Southern blot hybridization. Results: Strong expression of the epithelial form and variant forms containing exons 11 or 12 of the CD44 gene, which conferred metastatic behavior to rat cells, was detected in primary and metastatic tumor tissues, whereas it was very weak or not detectable in normal colonic mucosae, normal liver tissue, or peripheral blood leukocytes. However, adenomatous colorectal polyps also showed as strong an expression of epithelial and variant forms of CD44 as primary and metastatic tumor tissues. Conclusions: These results suggest that variant forms of CD44-mRNA might be expressed in an early stage of colorectal carcinogene- sis. 1 10). 10,11 One is expressed in hematopoietic cells with a molecular weight of kilodaltons and represents the basic unit of the CD44 proteins, the so-called hematopoietic or standard form. 4,6 Exons 6 15 are all spliced in this form of CD44. Another isoform, called the epithelial form, 4,6 is a protein with a molecular weight of kilodaltons, expressed weakly in normal epithelium but strongly in some carcinomas, which contains 135 amino acids more than the hematopoietic form in the extracellular portion of the molecule near the transmembrane region. Exons 6 12 are spliced in this form of CD44. Other variant forms are created by alternative splicing of the mrna and the addition of new exons to the extracellular domain near the transmembrane region of the hematopoietic form. Analysis of the comple- mentary DNA sequence of variant CD44 molecules, which is expressed on the surface of the metastatic rat pancreatic carcinoma cell line, has shown that the protein product of exons 11 and 12 (variant exons 6 and 7) of the CD44 gene is involved in the epitope of the metastasis of cancer cells and is sufficient to confer metastatic potential to nonmeta- static rodent cancer cells. 12,13 The expression of CD44 variant forms has been described in various human cancers, such as non-hodgkin s lymphoma, 14 breast cancers, 15 colorectal cancers, gastric cancers, 19,20 and uterine cervical cancers 21 by immunohistochemistry or reverse transcription polymerase chain reaction (RT-PCR). We report that CD44 splice variants are expressed in adenomatous polyps as much as in colorectal cancers by RT-PCR, suggesting that the expression of CD44 variant forms could be an early event in colorectal carcinogenesis. Materials and Methods Tumors and Tissues A total of 97 specimens were examined. Sixty-eight specimens obtained during surgical resection from 33 patients Abbreviations used in this paper: E/H ratio, epithelial/hematopoi- etic form ratio; RT-PCR, reverse transcription polymerase chain reac- tion by the American Gastroenterological Association /96/$3.00

2 February 1996 CD44-mRNA IN COLORECTAL CANCERS AND ADENOMAS 363 Figure 1. Schematic representation of the CD44 gene., Hematopoietic (standard) CD44;, exons that are spliced alternatively; Ø, untranslated regions;, transmembrane region. Exons 6 15 corre- spond to variant exons The location and direction of P1 and P2 oligonucleotide primers used for RT-PCR and P3, P4, and P5 for hybridization probe are shown. 37 C. The complementary DNA products were then used as templates for PCR in 100 ml volume of the reaction mixture containing 10 mmol/l Tris-HCl (ph 8.3), 50 mmol/l KCl, 1.5 mmol/l MgCl 2, 0.1 mmol/l deoxyribonucleoside triphosphate, 1 mmol/l primers P1 (5 -GACACATATTGCTTC- AATGCTTCAGC-3 ) (Figure 1), and P2. Amplification was performed with 2.5 U of Ampli-Taq polymerase (Takara Shuzo Corp., Shiga, Japan) in a DNA thermal cycler 480 (Perkin Elmer Cetus Corp., Norwalk, CT) after an initial 5-minute 94 C denaturation step, by 30 cycles of denaturation at 94 C for 1 minute, annealing at 55 C for 1 minute, and elongation at 72 C for 2 minutes. 15,24 Negative controls without total RNA in the reaction mixture were reverse-transcribed, followed by PCR amplification with every batch. Southern Blot Hybridization The PCR products were electrophoresed on 1.2% agarose gel and transferred to Hybond N / (Amersham In- (average age, 60 years) with colorectal cancer or liver metastasis ternational, Little Chalfont, Buckinghamshire, England) included 27 primary tumors, 1 polyp, 23 corresponding nor- nylon membranes for consecutive hybridization with mal colon mucosae, 9 metastatic liver tumors, and 8 corre- 32 P-labeled oligonucleotide probes P5 (5 -TGAGATTGGsponding normal liver tissue specimens (Table 1). Patients 1 GTTGAAGAAATC-3 ), P4 (5 -CCAGGCAACTCCTAG- 24 were without liver metastasis at the time of surgery. Pa- TAGTACAA-3 ), and P3 (5 -CCTGAAGAAGATTGTtients had liver metastasis at the time of surgery, and ACATCAGTCACAGAC-3 ). The locations of these both primary and metastatic tumors were analyzed. Metastatic primers are shown in Figure 1. Hybridization was perliver tumors only were obtained from patients whose formed using Rapid-Hyb buffer (Amersham), and the filprimary colorectal tumors had been resected 1 3 years earlier. ters were exposed to Kodak XAR-5 film with an intensi- Twenty-two specimens obtained during colonofiberscopy from fying screen, followed by immersion in boiling water for 11 patients (average age, 61 years) with colon polyps included 5 minutes before rehybridization with another probe. Two 5 adenocarcinomas, 15 adenomas, and 2 normal colon mucosae bands corresponding to hematopoietic and epithelial forms (Table 2). All of these samples were frozen quickly after exci- were quantitated with an Image Analyzer BAS 2000 (Fujix, sion and stored at 080 C until use. In addition, normal periph- Tokyo, Japan), and the ratio of the epithelial form to the eral blood leukocytes were obtained from 7 healthy volunteers. hematopoietic form (E/H ratio) was calculated. Statistical Tumorous and nontumorous parts of tissues and polyps were analysis was performed with the Wilcoxon s rank sum test. also fixed in 10% formalin and stained with H&E for histological examination. Colorectal carcinomas were staged according Results to the TNM classification 22 and histologically according to the Expression of CD44-mRNA in Colorectal degree of dysplasia in the polyps from mild to severe; the Tumors and Normal Colonic Mucosae histological grade of the carcinomas ranged from well differentiated to poorly differentiated. The clinical and pathological RNA was amplified with RT-PCR and hybridized features of these patients are described in Tables 1 and 2. with exon-specific probes to analyze the difference of RT-PCR Amplification expression of CD44-mRNA between tumors and normal tissues. Using primers P1 and P2, located 5 upstream Total cellular RNA was extracted from tumorous and and 3 downstream of the insertion site of the variant nontumorous tissues by the method of Chomezynski and Sac- exons (Figure 1), the 0.48-kilobase PCR product, indicachi. 23 Two micrograms of total RNA was used as a template tive of the hematopoietic form, was detected with a P3 for the synthesis of complementary DNA in reactions that oligonucleotide probe both in tumors and normal tissues. comprised 20 mmol/l Tris-HCl (ph 8.4), 50 mmol/l KCl, In contrast, several additional splice variants could be 2.5 mmol/l MgCl 2, 0.1 mg/ml bovine serum albumin, 0.5 amplified from primary and metastatic tumors (Figure mmol/l deoxyribonucleoside triphosphate, and 10 mmol/l dithiothreitol. First-strand synthesis was performed for 50 minthe epithelial form was amplified more frequently from 2A). The 0.88-kilobase PCR product corresponding to utes at 42 C in the presence of 200 U of SuperScript reverse transcriptase (GIBCO BRL Life Technologies, Inc., Gaithers- tumor specimens than from normal tissues (Figure 2A). burg, MD) with the specific primer P2 (5 -GATGCCAAG- The ratios of the epithelial to the hematopoietic form ATGATCAGCCATTCTGGAAT-3 ) (Figure 1) followed by (E/H) of CD44 were examined for a quantitative determinaincubation with 2 U of ribonuclease H for 20 minutes at tion of the epithelial form, one of the variant forms, in

3 364 IMAZEKI ET AL. GASTROENTEROLOGY Vol. 110, No. 2 Table 1. Clinicopathologic Characteristics of Patients With Colorectal Cancer E/H ratio Patient Age (yr)/sex Site Size (mm) Clinical stage a Histology T b M c N d 1 49/M Sigma Villotubular /M Rectum Well e /M Sigma Well /F Rectum Well /F Ascending Moderately f /M Descending Moderately 0.2 ND g 7 78/M Ascending Moderately /M Sigma Moderately /F Sigma Moderately /F Sigma Moderately /F Rectum Moderately /M Sigma Well /M Rectum Moderately 0.2 ND 14 79/M Sigma Well /F Cecum Moderately /M Transverse Moderately /F Rectum Moderately /M Sigma Moderately /M Sigma Well /F Ascending Well /F Cecum Moderately 0.5 ND 22 52/F Rectum Well 0 ND 23 61/M Sigma Moderately /M Sigma Moderately /M Sigma Moderately /F Ascending Moderately /F Sigma Mucinous /M Liver h ND 1.6 ND 29 52/M Liver ND 0.2 ND 30 55/F Liver ND 0.8 ND 31 38/M Liver ND 1.4 ND 32 57/M Liver ND 1.1 ND 33 69/M Liver ND 0.7 ND a Staged according to the TNM classification 22 : 0, carcinoma in situ; 1, tumor invades submucosa or muscularis propria without regional lymphnode and distant metastasis; 2, tumor invades through muscularis propria or perforates visceral peritoneum or directly invades other organs without regional lymphnode and distant metastasis; 3, tumor with regional lymphnode metastasis but no distant metastasis; 4, tumor with distant metastasis. b Primary colon cancer. c Metastatic liver tumor. d Nontumorous colon epithelium. e Well-differentiated adenocarcinoma. f Moderately differentiated adenocarcinoma. g Not done. h Metastasis. from whom specimens representing primary tumors and corresponding normal tissue specimens were simultaneously analyzed, displayed higher E/H ratios in their primary tumors than in their normal mucosae, and none of the 23 patients revealed higher E/H ratios in normal mucosae than in colorectal tumor tissue. We studied the correlation be- tween this E/H ratio and tumor size and clinical stage and histological grade. The E/H ratio was 0.6 { 0.5 in the tumor that was õ6 cmand0.8{ 0.6 in the tumor that was ú6 cm(p Å NS). The E/H ratio was 0.8 { 0.6 in stages 1 and 2 compared with 0.6 { 0.4 in stages 3 and 4(P Å NS). The E/H ratio was 1.0 { 0.6 in the well- primary and metastatic tumors and normal tissues. The mean values of E/H ratios in primary tumors, metastatic tumors, and normal colon mucosae were 0.7 { 0.5, 0.7 { 0.6, and 0.1 { 0.2, respectively, with both primary and metastatic tumors revealing higher ratios than normal mucosae (P õ 0.001). The liver metastatic tumor specimens displayed almost the same E/H ratios as the primary tumor specimens (Figure 3) and showed rather lower ratios than the primary tumor specimens in 3 patients from whom specimens representing normal mucosae, primary tumors, and liver metastatic tissue specimens were all simultaneously available (Figure 2A). Nineteen of 23 patients (83%),

4 February 1996 CD44-mRNA IN COLORECTAL CANCERS AND ADENOMAS 365 Table 2. Clinicopathologic Characteristics of Patients With Colorectal Polyps E/H ratio Patient Age (yr)/sex Site Size (mm) Histology P b N c 34 33/M Transverse Adenoma (mild) a 0.9 ND d 35 61/M Cecum Adenoma (moderate) 1.6 ND Transverse Adenoma (severe) 0.9 ND 36 61/M Rectum Adenoma (moderate) 1.4 ND 37 61/F Ascending Adenoma (mild) 1.9 ND Transverse Adenoma (mild) 2.9 ND Rectum Adenoma (severe) 2.1 ND 38 63/M Cecum Adenoma (mild) 1.9 ND Ascending Adenoma (mild) 2.0 ND 39 56/M Transverse Adenoma (moderate) /M Sigma Adenocarcinoma 1.9 ND 41 63/M Sigma Adenocarcinoma 1.4 ND 42 68/M Sigma Adenocarcinoma 1.8 ND Rectum Adenoma (mild) 0.8 ND 43 63/M Ascending Adenocarcinoma /M Ascending Adenocarcinoma 2.6 ND Transverse Adenoma (moderate) 3.1 ND Sigma Adenoma (moderate) 2.8 ND Sigma Adenoma (severe) 1.3 ND Sigma Adenoma (moderate) 1.9 ND a Parentheses show the degree of dysplasia in adenoma tissue. b Colon polyp. c Corresponding normal colon mucosa. d Not done. differentiated type and 0.5 { 0.4 in the moderately differen- fiberscopy, with 5 patients showing focal adenocarcinomas tiated type (P õ 0.05). and the other 15 showing adenomas (Table 2). The Hybridization with primers P4 and P5, located at expression of CD44-mRNA was also examined in these exons 11 and 12, respectively (Figure 1), showed that samples and, interestingly, the epithelial form and splic- the PCR products at 1.15 kilobases and larger sizes were ing variant forms containing exons 11 and 12 were detected easily detectable in primary and metastatic tumor tissues in addition to the hematopoietic form not only in but were only very weakly detectable or not detectable the early cancers but also in the adenomas (Figure 3A in normal tissues (Figure 2B and C). The expression of C and Table 2). Normal colon mucosae obtained from these variant forms correlated well with that of the epi- patients 39 and 43 displayed only the hematopoietic thelial form. No differential expression was shown in form (lane 9 in Figure 3A C). primary tumors without liver/lymph node metastasis and The E/H ratios were determined in these samples. with metastasis (lanes 1 and 3 vs. lanes 5, 7, and 9 in Their average in the adenomas with mild, moderate, and Figure 2). severe dysplasia and in the adenocarcinomas was 1.7 { Patient 24 had colorectal cancer with familial adenomatous 0.8, 2.0 { 0.7, 1.4 { 0.6, and 1.9 { 0.4, respectively; polyposis, and 1 of the multiple polyps, 15 mm that in the adenomas of õ10 mm and ú10 mm in in diameter, was analyzed for CD44-mRNA. The expression diameter was 1.9 { 0.9 and 1.7 { 0.6, respectively of CD44-mRNA in this polyp, with no evidence of (P Å NS). There was no correlation between these ratios cancer, was as strong as in the corresponding primary and histological grade (degree of dysplasia) or polyp size. tumor (data not shown). Peripheral blood leukocytes and The expression of alternative splicing variants also normal liver specimens expressed the hematopoietic form showed no correlation with the degree of dysplastic of CD44 but not the epithelial form or splicing variants change of the polyps (Figure 3A C). Some of the samples (Figure 2A C). were analyzed in duplicate from RNA extraction and the Expression of CD44-mRNA in Colorectal results were reproducible (data not shown). Polyps Discussion Twenty colorectal polyps ranging from 3 to 20 Our study showed that the expression of CD44 mm in size were obtained from 11 patients during colono- in colorectal carcinomas differed dramatically from that

5 366 IMAZEKI ET AL. GASTROENTEROLOGY Vol. 110, No. 2 in normal mucosae, but there was no differential expression in benign adenomatous polyps, malignant colorectal tumors, or metastatic liver tumors. The combination of RT-PCR and Southern blot hybridization provides a very sensitive method for analyzing the alternative splicing isoforms of CD44, but it does not allow for the precise quantification of various isoforms. Then, the E/H ratios of CD44 were calculated to quantitate the level of the epithelial form, one of the variant forms of CD44, as shown by Tanabe et al. 17 The E/H ratios in colorectal cancer were higher than those in corresponding normal mucosae in 19 of 23 cases (83%), but the epithelial form or splicing variant forms were detected to a lesser extent Figure 2. Analysis of CD44-mRNA in colorectal cancer by RT-PCR and Southern blot hybridization. Amplified products were electrophoresed on 1.2% agarose gel, and, after transfer to Hybond N / membranes, Figure 3. Analysis of CD44-mRNA in colorectal polyp by RT-PCR and the same filters were hybridized consecutively with (C) primer P5, (B) Southern blot hybridization. Amplified products were examined in the primer P4, and (A) primer P3 probes. T, primary colorectal tumor; N, same way as in Figure 2. Consecutive hybridization probes were (C) normal colorectal mucosa; M, metastatic liver tumor; L, normal liver; primer P5, (B) primer P4, and (A) primer P3. n, normal colon mucosa; PBL, peripheral blood leukocytes from normal volunteers. E, epithelial m, mild dysplasia; mo, moderate dysplasia; s, severe dysplasia; ca, form of CD44; H, hematopoietic form of CD44. Lanes 1 and 2, patient adenocarcinoma. E, epithelial form of CD44; H, hematopoietic form 4; lanes 3 and 4, patient 9; lanes 5 and 6, patient 14; lanes 7 and of CD44. Lane 1, patient 36; lanes 2 4, patient 37; lane 5, patient 8, patient 17; lanes 9 12, patient 25; lane 13, patient 30; lane 14, 41; lanes 6 and 7, patient 42; lanes 8 and 9, patient 43; lanes 10 patient , patient 44.

6 February 1996 CD44-mRNA IN COLORECTAL CANCERS AND ADENOMAS 367 ant exon 7) was present in early adenoma but had no correlation with colorectal tumor progression. Dis- cordance between the expressions of mrna and the protein product may be involved in these differences of CD44 expression, as also reported in the keratin gene expression in the salivary gland. 27 The hematopoietic form is the most widely expressed type of CD44 and has been shown to be a major cell surface receptor for hyaluronate. 4 It has been discussed that the hyaluronate binding activity of CD44 on some T cells was induced by a CD44-specific antibody, 28 suggesting that physiological mechanisms may exist for the activation of CD44 function. Although the precise role and the regulation of the CD44 variants remain to be defined, a similar process might be involved in the induc- tion of variant CD44 activation. Guo et al. 29 reported that the concentration of soluble CD44 in serum was elevated in patients with advanced colon cancer and correlated with tumor metastasis and tumor burden. If elevated CD44 levels in the serum would be related to tumor volume rather than metastasis and there was no differential expression of CD44 in benign adenomatous polyps and malignant colorectal tu- mors, patients with familial adenomatous polyposis, with no evidence of cancer, may have elevated serum CD44 levels to the same degree as patients with colon cancer. Mulder et al. 30 reported that the expression of the rat metastasis-related variant of CD44 (exon v6) in colon tumors by immunohistochemistry was associated with an unfavorable prognosis. Finn et al. 31 also showed by RT-PCR assay that increasing levels of variant CD44 forms were associated with poor survival. However, CD44v6 expression and variant molecules of CD44 were detected in adenomatous polyps by immunohistochemis- try and Western blotting. 16,26 By the RT-PCR method, we also showed the overexpression of variant CD44 at the stage of benign adenomatous polyps that precedes colorectal cancer. The mechanism of CD44 production remains to be clarified. The extensive genomic alterations seen in colo- rectal tumors might cause the variant mrna of CD44, although various isoforms of CD44 are suggested to be generated by an alternative splicing mechanism. 10,11 Analysis of genomic DNA from matched pairs of colon cancer and normal colon mucosa by Southern blot hybridization may very well confirm that the variant mrna is caused by splicing rather than genomic dele- tion or rearrangement. In conclusion, our result suggests that the expression of the CD44 variants could be an early event in colorectal carcinogenesis similar to the genetic changes of APC or K-ras genes that have been exemplified in the colorectal in 10 of 23 (43%) normal colon mucosae, indicating that the expression of these variant forms is not specific for cancer. 15,17,25 Interestingly, the E/H ratios in adenomatous polyps showed no difference from those in colorectal cancers (Figure 3A and Table 2), and the level of these ratios was not different among primary tumors with liver/ lymph node metastasis (stages 3 and 4) or without metastasis (stages 1 and 2) and liver metastatic specimens (Figure 2A and Table 1). Hence, the overexpression of the epithelial form was not specific for primary cancer or for metastasis. The E/H ratios were different for the studies on cancers and adenomas, approximately 0.7 for the former and 1.8 for the latter. This was because CD44 expression in the study of polyps showed a decrease in hematopoietic form rather than an increase in epithelial form and some variant forms (Figure 3A), although the reason for this is not clear. The result was reproducible when we examined several samples of cancers and polyps simultaneously from RT-PCR in the same batch by Southern blot hy- bridization on the same filter (data not shown). Our study showed that the E/H ratio in well-differentiated colorectal cancer was higher than that in the moderately differentiated type. Our results are compatible with the report by Kim et al. 26 that variant molecules of CD44 were detected more frequently in the adenomatous portions than in the accompanying carcinomas in the study of colorectal adenomas. Matsumura et al. 15 reported that there was a marked difference in the number and size of the bands and the intensity of the signal containing an exon-12 (variant exon 7) sequence with RT-PCR among samples from liver metastatic tumors and primary tumors with metastasis or without metastasis. Our results using RT-PCR showed that CD44 containing an exon-11 or exon-12 sequence had no differential expression in metastatic tu- mors or in primary tumors with or without liver/lymph node metastasis. Our results also indicated that the size and number of the signals containing exon 11 were identical to those containing exon 12 in the cases of colorectal cancers and adenomas (Figures 2 and 3). Because we could not differentiate the adenomatous polyp from can- cer by the intensity and size of the bands of variant CD44, analysis of clinical samples for CD44 variants by RT-PCR is unlikely to be of practical value for cancer diagnosis. Wielenga et al. 18 showed immunohistochemically that the overexpression of CD44 isoforms carrying epitopes of exon 11 (variant exon 6) was well correlated with the progression of colorectal tumors, i.e., with the severity of dysplasia in adenoma and with Dukes stage in invasive carcinoma. They also reported that the expression of CD44 carrying epitopes encoded by exon 12 (vari-

7 368 IMAZEKI ET AL. GASTROENTEROLOGY Vol. 110, No. 2 adenoma-carcinoma sequence, 32 and a novel expression cancer diagnosis and disease evaluation. Lancet 1992; 340: of the CD44 gene at an early stage of carcinogenesis 16. Heider K-H, Hofmann M, Hors E, van den Berg F, Ponta H, Herrlich might provide favorable conditions for cell proliferation. P, Pals ST. A human homologue of the rat metastasis-associated variant of CD44 is expressed in colorectal carcinomas and adenomatous polyps. J Cell Biol 1993;120: References 17. Tanabe KK, Ellis LM, Saya H. Expression of CD44R1 adhesion 1. Jalkanen S, Bargatze RF, de los Toyos J, Butcher EC. Lymphocyte molecule in colon carcinomas and metastases. Lancet 1993; recognition of high endothelium: antibodies to distinct epitopes 341: of an kd glycoprotein antigen differentially inhibit lympho- 18. Wielenga VJM, Heider K-H, Offerhaus GJA, Adolf GR, van den cyte binding to lymphnode, mucosal, or synovial endothelial cells. Berg FM, Ponta H, Herrlich P, Pals ST. Expression of CD44 variant J Cell Biol 1987;105: proteins in human colorectal cancers is related to tumor progres- 2. Carter WG, Wayner EA. Characterization of the class III collagen sion. Cancer Res 1993;53: receptor, a phosphorylated, transmembrane glycoprotein ex- 19. Heider K-H, Dammrich J, Skroch Angel P, Muller Hermelink H, pressed in nucleated human cells. J Biol Chem 1989;263: Vollmers HP, Herrlich P, Ponta H. Differential expression of CD splice variants in intestinal- and diffuse-type human gastric carci- 3. Jalkanen S, Jalkanen M. Lymphocyte CD44 binds the COOHnomas and normal gastric mucosa. Cancer Res 1993;53:4197 terminal heparin-binding domain of fibronectin. J Cell Biol ;116: Mayer B, Jauch KW, Gunthert U, Figdor CG, Schildberg FW, Funke I, Johnson JP. De-novo expression of CD44 and survival in gastric 4. Stamenkovic I, Aruffo A, Amiot M, Seed B. The hematopoietic and cancer. Lancet 1993;342: epithelial forms of CD44 are distinct polypeptides with different 21. Peter D, Heider K-H, Hekele A, von Minckwitz G, Kaufmann M, adhesion potentials for hyaluronate-bearing cells. EMBO J Ponta H, Herrlich P. Surface protein expression and messenger 1991;10: RNA-splicing analysis of CD44 in uterine cervical cancer and nor- 5. Koopman GY, van Kooyk Y, de Graaff M, Meyer CJLM, Figdor mal cervical epithelium. Cancer Res 1994;54: CG, Pals ST. Triggering of the CD44 antigen on T lymphocytes 22. Beahrs OH, Henson DE, Hutter RVP, Myers MH. Manual for stagpromotes T cell adhesion through the LFA-1 pathway. J Immunol ing of cancer. 3rd ed. Philadelphia: Lippincott, 1988: ;145: Chomczynski P, Sacchi N. Single-step method of RNA isolation 6. Stamenkovic I, Amiot M, Pasedo JM, Seed B. A lymphocyte mole- by acid guanidinium thiocyanate phenol-chloroform extraction. cule implicated in lymph node homing is a member of the carti- Anal Biochem 1987;162: lage link protein family. Cell 1989;56: Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, 7. Jalkanen S, Jalkanen M, Bargatze R, Tammi M, Butcher EC. Bio- Mullis KB, Erlich HA. Primer-directed enzymatic amplification of chemical properties of glycoproteins involved in lymphocyte rec- DNA with a thermostable DNA polymerase. Science 1988; ognition of high endothelial venules in man. J Immunol 1988; 239: : Fox SB, Gatter K, Jackson DG, Screaton GR, Bell MV, Bell JI, 8. Screaton GR, Bell MV, Jackson DG, Cornelis FB, Gerth U, Bell Harris AL, Simmonds D, Fawcett J. CD44 and cancer screening. JI. Genomic structure of DNA encoding the lymphocyte homing Lancet 1993;342: receptor CD44 reveals at least 12 alternatively spliced exons. 26. Kim H, Yang X-L, Rosada C, Hamilton SR, August JT. CD44 ex- Proc Natl Acad Sci USA 1992;89: pression in colorectal adenomas is an early event occurring prior 9. Tolg C, Hofmann M, Herrlich P, Ponta H. Splicing choice from ten to K-ras and p53 gene mutation. Archives Biochem Biophys variant exons establishes CD44 variability. Nucleic Acids Res 1994;310: ;21: Su L, Morgan PR, Harrison DL, Waseem A, Lane EB. Expression 10. Jackson DG, Buckley J, Bell JI. Multiple variants of the human of keratin m-rnas and proteins in normal salivary epithelia and lymphocyte homing receptor CD44 generated by insertions at a pleomorphic adenomas. J Pathol 1993;171: single site in the extracellular domain. J Biol Chem 1992; 28. Lesley J, He Q, Miyake K, Hamann A, Hyman R, Kincade PW. 267: Requirements for hyaluronic acid binding by CD44: a role for 11. Hofmann M, Rudy W, Zoller M, Tolg C, Ponta H, Herrlich P, Gunththe cytoplasmic domain and activation by antibody. J Exp Med 1992;175: ert U. CD44 splice variants confer metastatic behavior in rats: 29. Guo Y-J, Liu G, Wang X, Jin D, Wu M, Ma J, Sy M-S. Potential homologous sequences are expressed in human tumor cell lines. use of soluble CD44 in serum as indicator of tumor burden and Cancer Res 1991;51: metastasis in patients with gastric or colon cancer. Cancer Res 12. Gunthert U, Hofmann M, Rudy W, Reber S, Zoller M, Haussman 1994;54: I, Matzku S, Wenzel A, Ponta H, Herrlich P. A new variant of 30. Mulder J-W R, Kruyt PM, Sewnath M, Oosting J, Seldenrijk CA, glycoprotein CD44 confers metastatic potential to rat carcinoma Weidema WF, Offerhaus GJA, Pals ST. Colorectal cancer prognocells. Cell 1991;65: sis and expression of exon-v6 containing CD44 proteins. Lancet 13. Rudy W, Hofmann M, Schwartz Albiez R, Zoller M, Heider K-H, 1994;344: Ponta H, Herrlich P. The two major CD44 proteins expressed on 31. Finn L, Dougherty G, Finley G, Meisler A, Becich M, Cooper DL. a metastatic rat tumor cell line are derived from different splice Alternative splicing of CD44 pre-mrna in human colorectal tuvariants: each one individually suffices to confer metastatic be- mors. Biochem Biophys Res Commun 1994;200: havior. Cancer Res 1993;53: Fearon ER, Vogelstein B. A genetic model for colorectal tumori- 14. Koopman G, Heider K-H, Horst E, Adolf GR, van den Berg F, genesis. Cell 1990;61: Ponta H, Herrlich P, Pals ST. Activated human lymphocytes and aggressive non-hodgkin s lymphomas express a homologue of Received February 6, Accepted September 25, the rat metastasis-associated variant of CD44. J Exp Med Address requests for reprints to: Fumio Imazeki, M.D., First Depart- 1993;177: ment of Medicine, Chiba University School of Medicine, Inohana Matsumura Y, Tarin D. Significance of CD44 gene products for 8-1, Chuou-ku, Chiba 260, Japan. Fax: (81)

CD44 glycoproteins in colorectal cancer; expression, function and prognostic value Wielenga, V.J.M.

CD44 glycoproteins in colorectal cancer; expression, function and prognostic value Wielenga, V.J.M. UvA-DARE (Digital Academic Repository) CD44 glycoproteins in colorectal cancer; expression, function and prognostic value Wielenga, V.J.M. Link to publication Citation for published version (APA): Wielenga,

More information

A916: rectum: adenocarcinoma

A916: rectum: adenocarcinoma General facts of colorectal cancer The colon has cecum, ascending, transverse, descending and sigmoid colon sections. Cancer can start in any of the r sections or in the rectum. The wall of each of these

More information

Histopathology: Colorectal polyps and carcinoma

Histopathology: Colorectal polyps and carcinoma Histopathology: Colorectal polyps and carcinoma These presentations are to help you identify, and to test yourself on identifying, basic histopathological features. They do not contain the additional factual

More information

Clinical significance of CD44 expression in children with hepatoblastoma

Clinical significance of CD44 expression in children with hepatoblastoma Clinical significance of CD44 expression in children with hepatoblastoma H.-Y. Cai 1 *, B. Yu 1 *, Z.-C. Feng 2, X. Qi 1 and X.-J. Wei 1 1 Department of General Surgery, General Hospital of Beijing Military

More information

CD44 glycoproteins in colorectal cancer; expression, function and prognostic value Wielenga, V.J.M.

CD44 glycoproteins in colorectal cancer; expression, function and prognostic value Wielenga, V.J.M. UvA-DARE (Digital Academic Repository) CD44 glycoproteins in colorectal cancer; expression, function and prognostic value Wielenga, V.J.M. Link to publication Citation for published version (APA): Wielenga,

More information

Wendy L Frankel. Chair and Distinguished Professor

Wendy L Frankel. Chair and Distinguished Professor 1 Wendy L Frankel Chair and Distinguished Professor Case 1 59 y/o woman Abdominal pain No personal or family history of cancer History of colon polyps Colonoscopy Polypoid rectosigmoid mass Biopsy 3 4

More information

Greater Manchester & Cheshire Guidelines for Pathology Reporting for Oesophageal and Gastric Malignancy

Greater Manchester & Cheshire Guidelines for Pathology Reporting for Oesophageal and Gastric Malignancy Greater Manchester & Cheshire Guidelines for Pathology Reporting for Oesophageal and Gastric Malignancy Authors: Dr Gordon Armstrong, Dr Sue Pritchard 1. General Comments 1.1 Cancer reporting: Biopsies

More information

Colorectal Cancer Structured Pathology Reporting Proforma DD MM YYYY

Colorectal Cancer Structured Pathology Reporting Proforma DD MM YYYY Colorectal Cancer Structured Pathology Reporting Proforma Mandatory questions (i.e. protocol standards) are in bold (e.g. S1.03). Family name Given name(s) Date of birth DD MM YYYY S1.02 Clinical details

More information

Senior Thesis. Presented to. The Faculty of the School of Arts and Sciences Brandeis University

Senior Thesis. Presented to. The Faculty of the School of Arts and Sciences Brandeis University Greenwald 1 Mouse intercellular adhesion molecule 1 (ICAM-1) isoforms demonstrate different binding affinities to mouse macrophage-1 antigen (Mac-1) and preliminary evidence for alternatively-spliced variants

More information

Bio 111 Study Guide Chapter 17 From Gene to Protein

Bio 111 Study Guide Chapter 17 From Gene to Protein Bio 111 Study Guide Chapter 17 From Gene to Protein BEFORE CLASS: Reading: Read the introduction on p. 333, skip the beginning of Concept 17.1 from p. 334 to the bottom of the first column on p. 336, and

More information

Dr Rodney Itaki Lecturer Anatomical Pathology Discipline. University of Papua New Guinea School of Medicine & Health Sciences Division of Pathology

Dr Rodney Itaki Lecturer Anatomical Pathology Discipline. University of Papua New Guinea School of Medicine & Health Sciences Division of Pathology Neoplasia Dr Rodney Itaki Lecturer Anatomical Pathology Discipline University of Papua New Guinea School of Medicine & Health Sciences Division of Pathology General Considerations Overview: Neoplasia uncontrolled,

More information

Urinary Bladder: WHO Classification and AJCC Staging Update 2017

Urinary Bladder: WHO Classification and AJCC Staging Update 2017 Urinary Bladder: WHO Classification and AJCC Staging Update 2017 Houston Society of Clinical Pathologists 58 th Annual Spring Symposium Houston, TX April 8, 2017 Jesse K. McKenney, MD Classification

More information

Update on staging colorectal carcinoma, the 8 th edition AJCC. General overview of staging. When is staging required? 11/1/2017

Update on staging colorectal carcinoma, the 8 th edition AJCC. General overview of staging. When is staging required? 11/1/2017 Update on staging colorectal carcinoma, the 8 th edition AJCC Dale C. Snover, MD November 3, 2017 General overview of staging Reason for uniform staging Requirements to use AJCC manual and/or CAP protocols

More information

Test Bank for Robbins and Cotran Pathologic Basis of Disease 9th Edition by Kumar

Test Bank for Robbins and Cotran Pathologic Basis of Disease 9th Edition by Kumar Link full download:https://getbooksolutions.com/download/test-bank-for-robbinsand-cotran-pathologic-basis-of-disease-9th-edition-by-kumar Test Bank for Robbins and Cotran Pathologic Basis of Disease 9th

More information

PD-L1 Analyte Control DR

PD-L1 Analyte Control DR Quality in Control PD-L1 Analyte Control DR PD-L1_PI_v2 Product Codes: HCL019, HCL020 and HCL021 Contents PD-L1 Analyte Control DR 2 What is PD-L1? 3 The Role of PD-L1 in Cancer 3 PD-L1 Assessment 4 PD-L1

More information

Disclosures. Outline. What IS tumor budding?? Tumor Budding in Colorectal Carcinoma: What, Why, and How. I have nothing to disclose

Disclosures. Outline. What IS tumor budding?? Tumor Budding in Colorectal Carcinoma: What, Why, and How. I have nothing to disclose Tumor Budding in Colorectal Carcinoma: What, Why, and How Disclosures I have nothing to disclose Soo-Jin Cho, MD, PhD Assistant Professor UCSF Dept of Pathology Current Issues in Anatomic Pathology 2017

More information

Chapter 13 Cancer of the Female Breast

Chapter 13 Cancer of the Female Breast Lynn A. Gloeckler Ries and Milton P. Eisner INTRODUCTION This study presents survival analyses for female breast cancer based on 302,763 adult cases from the Surveillance, Epidemiology, and End Results

More information

Peritoneal Involvement in Stage II Colon Cancer

Peritoneal Involvement in Stage II Colon Cancer Anatomic Pathology / PERITONEAL INVOLVEMENT IN STAGE II COLON CANCER Peritoneal Involvement in Stage II Colon Cancer A.M. Lennon, MB, MRCPI, H.E. Mulcahy, MD, MRCPI, J.M.P. Hyland, MCh, FRCS, FRCSI, C.

More information

LOINC. Clinical information. RCPA code. Record if different to report header Operating surgeon name and contact details. Absent.

LOINC. Clinical information. RCPA code. Record if different to report header Operating surgeon name and contact details. Absent. Complete as narrative or use the structured format below 55752-0 17.02.28593 Clinical information 22027-7 17.02.30001 Record if different to report header Operating surgeon name and contact details 52101004

More information

The Role of CCR9 and Melanoma Metastasis to Small Intestine. Farin Amersi, MD Samuel Oschin Comprehensive Cancer Center Cedar Sinai Medical Center

The Role of CCR9 and Melanoma Metastasis to Small Intestine. Farin Amersi, MD Samuel Oschin Comprehensive Cancer Center Cedar Sinai Medical Center The Role of CCR9 and Melanoma Metastasis to Small Intestine Farin Amersi, MD Samuel Oschin Comprehensive Cancer Center Cedar Sinai Medical Center BACKGROUND Melanoma is the fifth most common cancer. Estimated

More information

Gastric Cancer Histopathology Reporting Proforma

Gastric Cancer Histopathology Reporting Proforma Gastric Cancer Histopathology Reporting Proforma Mandatory questions (i.e. protocol standards) are in bold (e.g. S1.01). S1.01 Identification Family name Given name(s) Date of birth Sex Male Female Intersex/indeterminate

More information

Colonic Polyp. Najmeh Aletaha. MD

Colonic Polyp. Najmeh Aletaha. MD Colonic Polyp Najmeh Aletaha. MD 1 Polyps & classification 2 Colorectal cancer risk factors 3 Pathogenesis 4 Surveillance polyp of the colon refers to a protuberance into the lumen above the surrounding

More information

Quiz. b. 4 High grade c. 9 Unknown

Quiz. b. 4 High grade c. 9 Unknown Quiz 1. 10/11/12 CT scan abdomen/pelvis: Metastatic liver disease with probable primary colon malignancy. 10/17/12 Colonoscopy with polypectomy: Adenocarcinoma of sigmoid colon measuring at least 6 mm

More information

Neoplastic Colon Polyps. Joyce Au SUNY Downstate Grand Rounds, October 18, 2012

Neoplastic Colon Polyps. Joyce Au SUNY Downstate Grand Rounds, October 18, 2012 Neoplastic Colon Polyps Joyce Au SUNY Downstate Grand Rounds, October 18, 2012 CASE 55M with Hepatitis C, COPD (FEV1=45%), s/p vasectomy, knee surgery Meds: albuterol, flunisolide, mometasone, tiotropium

More information

The Incidence and Significance of Villous Change in Adenomatous Polyps

The Incidence and Significance of Villous Change in Adenomatous Polyps The Incidence and Significance Villous Change in Adenomatous Polyps CHRISTOPHER H. K. FUNC, M.D., AND HARVEY GOLDMAN, M.D. Department Pathology, Harvard Medical School and Beth Israel Hospital, Boston,

More information

Identification of Novel Variant of EML4-ALK Fusion Gene in NSCLC: Potential Benefits of the RT-PCR Method

Identification of Novel Variant of EML4-ALK Fusion Gene in NSCLC: Potential Benefits of the RT-PCR Method International journal of Biomedical science ORIGINAL ARTICLE Identification of Novel Variant of EML4-ALK Fusion Gene in NSCLC: Potential Benefits of the RT-PCR Method Martin K. H. Maus 1, 2, Craig Stephens

More information

Expression and significance of Bmi-1 and Ki67 in colorectal carcinoma tissues

Expression and significance of Bmi-1 and Ki67 in colorectal carcinoma tissues [Chinese Journal of Cancer 27:12, 568-573; December Expression 2008]; 2008 and significance Sun Yat-sen of University Bmi-1 and Cancer Ki67 in Center colorectal carcinoma tissues Clinical Research Paper

More information

AJCC 8 th edition update*: Colorectal cancer

AJCC 8 th edition update*: Colorectal cancer AJCC 8 th edition update*: Colorectal cancer Dr Caroline Cooper Pathology Queensland- Princess Alexandra Hospital, Brisbane * and other prognostic controversies Chapter 20 Colorectal adenocarcinoma High

More information

Detection and Clinical Significance of Lymph Node Micrometastasis in Gastric Cardia Adenocarcinoma

Detection and Clinical Significance of Lymph Node Micrometastasis in Gastric Cardia Adenocarcinoma The Journal of International Medical Research 2012; 40: 293 299 [first published online ahead of print as 40(1) 3] Detection and Clinical Significance of Lymph Node Micrometastasis in Gastric Cardia Adenocarcinoma

More information

Disorders of Cell Growth & Neoplasia. Histopathology Lab

Disorders of Cell Growth & Neoplasia. Histopathology Lab Disorders of Cell Growth & Neoplasia Histopathology Lab Paul Hanna April 2010 Case #84 Clinical History: 5 yr-old, West Highland White terrier. skin mass from axillary region. has been present for the

More information

GOBLET CELL CARCINOID

GOBLET CELL CARCINOID GOBLET CELL CARCINOID Hanlin L. Wang, MD, PhD University of California Los Angeles Disclosure of Relevant Financial Relationships USCAP requires that all planners (Education Committee) in a position to

More information

Primary enteric adenocarcinoma with predominantly signet ring features of the lung: A case report with clinicopathological and molecular findings

Primary enteric adenocarcinoma with predominantly signet ring features of the lung: A case report with clinicopathological and molecular findings CASE REPORT Primary enteric adenocarcinoma with predominantly signet ring features of the lung: A case report with clinicopathological and molecular findings Makoto Nagashima 1, Ayako Moriyama 1, Yasuo

More information

Regulation of Gene Expression in Eukaryotes

Regulation of Gene Expression in Eukaryotes Ch. 19 Regulation of Gene Expression in Eukaryotes BIOL 222 Differential Gene Expression in Eukaryotes Signal Cells in a multicellular eukaryotic organism genetically identical differential gene expression

More information

TUMOR M ARKERS MARKERS

TUMOR M ARKERS MARKERS TUMOR MARKERS M.Shekarabi IUMS Definition Many cancers are associated with the abnormal production of some molecules l which h can be measured in plasma. These molecules are known as tumor markers. A good

More information

Coordinate Expression of Cytokeratins 7 and 20 in Prostate Adenocarcinoma and Bladder Urothelial Carcinoma

Coordinate Expression of Cytokeratins 7 and 20 in Prostate Adenocarcinoma and Bladder Urothelial Carcinoma Anatomic Pathology / CYTOKERATINS 7 AND 20 IN PROSTATE AND BLADDER CARCINOMAS Coordinate Expression of Cytokeratins 7 and 20 in Prostate Adenocarcinoma and Bladder Urothelial Carcinoma Nader H. Bassily,

More information

Patologia sistematica V Gastroenterologia Prof. Stefano Fiorucci. Colon polyps. Colorectal cancer

Patologia sistematica V Gastroenterologia Prof. Stefano Fiorucci. Colon polyps. Colorectal cancer Patologia sistematica V Gastroenterologia Prof. Stefano Fiorucci Colon polyps Colorectal cancer Harrison s Principles of Internal Medicine 18 Ed. 2012 Colorectal cancer 70% Colorectal cancer CRC and colon

More information

oncogenes-and- tumour-suppressor-genes)

oncogenes-and- tumour-suppressor-genes) Special topics in tumor biochemistry oncogenes-and- tumour-suppressor-genes) Speaker: Prof. Jiunn-Jye Chuu E-Mail: jjchuu@mail.stust.edu.tw Genetic Basis of Cancer Cancer-causing mutations Disease of aging

More information

SAMs Guidelines DEVELOPING SELF-ASSESSMENT MODULES TEST QUESTIONS. Ver. #

SAMs Guidelines DEVELOPING SELF-ASSESSMENT MODULES TEST QUESTIONS. Ver. # SAMs Guidelines DEVELOPING SELF-ASSESSMENT MODULES TEST Ver. #5-02.12.17 GUIDELINES FOR DEVELOPING SELF-ASSESSMENT MODULES TEST The USCAP is accredited by the American Board of Pathology (ABP) to offer

More information

Neoplasia part I. Dr. Mohsen Dashti. Clinical Medicine & Pathology nd Lecture

Neoplasia part I. Dr. Mohsen Dashti. Clinical Medicine & Pathology nd Lecture Neoplasia part I By Dr. Mohsen Dashti Clinical Medicine & Pathology 316 2 nd Lecture Lecture outline Review of structure & function. Basic definitions. Classification of neoplasms. Morphologic features.

More information

Carcinoembryonic Antigen

Carcinoembryonic Antigen Other Names/Abbreviations CEA 190.26 - Carcinoembryonic Antigen Carcinoembryonic antigen (CEA) is a protein polysaccharide found in some carcinomas. It is effective as a biochemical marker for monitoring

More information

Carcinoembryonic Antigen

Carcinoembryonic Antigen Other Names/Abbreviations CEA 190.26 - Carcinoembryonic Antigen Carcinoembryonic antigen (CEA) is a protein polysaccharide found in some carcinomas. It is effective as a biochemical marker for monitoring

More information

Supplementary Figure 1. HOPX is hypermethylated in NPC. (a) Methylation levels of HOPX in Normal (n = 24) and NPC (n = 24) tissues from the

Supplementary Figure 1. HOPX is hypermethylated in NPC. (a) Methylation levels of HOPX in Normal (n = 24) and NPC (n = 24) tissues from the Supplementary Figure 1. HOPX is hypermethylated in NPC. (a) Methylation levels of HOPX in Normal (n = 24) and NPC (n = 24) tissues from the genome-wide methylation microarray data. Mean ± s.d.; Student

More information

Hepatitis B Antiviral Drug Development Multi-Marker Screening Assay

Hepatitis B Antiviral Drug Development Multi-Marker Screening Assay Hepatitis B Antiviral Drug Development Multi-Marker Screening Assay Background ImQuest BioSciences has developed and qualified a single-plate method to expedite the screening of antiviral agents against

More information

NPQR Quality Payment Program (QPP) Measures 21_18247_LS.

NPQR Quality Payment Program (QPP) Measures 21_18247_LS. NPQR Quality Payment Program (QPP) Measures 21_18247_LS MEASURE ID: QPP 99 MEASURE TITLE: Breast Cancer Resection Pathology Reporting pt Category (Primary Tumor) and pn Category (Regional Lymph Nodes)

More information

COLORECTAL CANCER: PROGNOSTIC VALUES

COLORECTAL CANCER: PROGNOSTIC VALUES & COLORECTAL CANCER: PROGNOSTIC VALUES Suzana Manxhuka-Kerliu¹*, Skender Telaku², Halil Ahmetaj³, Arijeta Baruti¹, Sadushe Loxha¹, Agron Kerliu³ ¹ Institute of Pathology, Faculty of Medicine, University

More information

How to Recognize Gynecologic Cancer Cells from Pelvic Washing and Ascetic Specimens

How to Recognize Gynecologic Cancer Cells from Pelvic Washing and Ascetic Specimens How to Recognize Gynecologic Cancer Cells from Pelvic Washing and Ascetic Specimens Wenxin Zheng, M.D. Professor of Pathology and Gynecology University of Arizona zhengw@email.arizona.edu http://www.zheng.gynpath.medicine.arizona.edu/index.html

More information

Definition of Synoptic Reporting

Definition of Synoptic Reporting Definition of Synoptic Reporting The CAP has developed this list of specific features that define synoptic reporting formatting: 1. All required cancer data from an applicable cancer protocol that are

More information

Template for Reporting Results of Biomarker Testing of Specimens From Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Template for Reporting Results of Biomarker Testing of Specimens From Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Template for Reporting Results of Biomarker Testing of Specimens From Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Version: CLLBiomarkers 1.0.0.2 Protocol Posting Date: June 2017

More information

Using of S100A9 as a Novel Biomarker for Early Detection of Colorectal Cancer, A Stool Based Study in Iraq

Using of S100A9 as a Novel Biomarker for Early Detection of Colorectal Cancer, A Stool Based Study in Iraq ISSN: 2319-7706 Volume 4 Number 10 (2015) pp. 138-145 http://www.ijcmas.com Original Research Article Using of S100A9 as a Novel Biomarker for Early Detection of Colorectal Cancer, A Stool Based Study

More information

SAM PROVIDER TOOLKIT

SAM PROVIDER TOOLKIT THE AMERICAN BOARD OF PATHOLOGY Maintenance of Certification (MOC) Program SAM PROVIDER TOOLKIT Developing Self-Assessment Modules (SAMs) www.abpath.org The American Board of Pathology (ABP) approves educational

More information

4/12/2018. MUSC Pathology Symposium Kiawah Island April 18, Jesse K. McKenney, MD

4/12/2018. MUSC Pathology Symposium Kiawah Island April 18, Jesse K. McKenney, MD MUSC Pathology Symposium Kiawah Island April 18, 2018 Jesse K. McKenney, MD 1 Urothelial Carcinoma with Alternative Differentiation 2 Urothelial Carcinoma with Alternative Differentiation Recognition as

More information

Higher expression of deoxyuridine triphosphatase (dutpase) may predict the metastasis potential of colorectal cancer

Higher expression of deoxyuridine triphosphatase (dutpase) may predict the metastasis potential of colorectal cancer 1 Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan; 2 Department of Surgery, Kurume University School of Medicine, Kurume, Japan; 3 Biostatistics Center, Kurume University,

More information

Pruritus Ani in an Elderly Man

Pruritus Ani in an Elderly Man Pruritus Ani in an Elderly Man Pedro Redondo, MD; Michel Idoate, MD; Agustín España, MD; Emilio Quintanilla, MD; University of Navarra, Pamplona, Spain REPORT OF A CASE A 78-year-old man presented with

More information

Key words: Collagen synthesis - N-Terminal peptide of type III procollagen - Tumor marker - Liver cancer - Liver cirrhosis

Key words: Collagen synthesis - N-Terminal peptide of type III procollagen - Tumor marker - Liver cancer - Liver cirrhosis [Gann, 75, 130-135; February, 1984] HIGH CONCENTRATIONS OF N-TERMINAL PEPTIDE OF TYPE III PROCOLLAGEN IN THE SERA OF PATIENTS WITH VARIOUS CANCERS, WITH SPECIAL REFERENCE TO LIVER CANCER Terumasa HATAHARA,

More information

Central Poorly Differentiated Adenocarcinoma of the Maxilla: Report of a Case

Central Poorly Differentiated Adenocarcinoma of the Maxilla: Report of a Case Kobe J. Med. Sci., Vol. 49, No. 2, pp. 45-49, 2003 Central Poorly Differentiated Adenocarcinoma of the Maxilla: Report of a Case MASAHIRO UMEDA 1), SATOSHI YOKOO 1), YASUYUKI SHIBUYA 1), TAKAHIDE KOMORI

More information

Characterization and significance of MUC1 and c-myc expression in elderly patients with papillary thyroid carcinoma

Characterization and significance of MUC1 and c-myc expression in elderly patients with papillary thyroid carcinoma Characterization and significance of MUC1 and c-myc expression in elderly patients with papillary thyroid carcinoma Y.-J. Hu 1, X.-Y. Luo 2, Y. Yang 3, C.-Y. Chen 1, Z.-Y. Zhang 4 and X. Guo 1 1 Department

More information

The Blueprint of Life: DNA to Protein. What is genetics? DNA Structure 4/27/2011. Chapter 7

The Blueprint of Life: DNA to Protein. What is genetics? DNA Structure 4/27/2011. Chapter 7 The Blueprint of Life: NA to Protein Chapter 7 What is genetics? The science of heredity; includes the study of genes, how they carry information, how they are replicated, how they are expressed NA Structure

More information

Bihong Zhao, M.D, Ph.D Department of Pathology

Bihong Zhao, M.D, Ph.D Department of Pathology Bihong Zhao, M.D, Ph.D Department of Pathology 04-28-2009 Is tumor self or non-self? How are tumor antigens generated? What are they? How does immune system respond? Introduction Tumor Antigens/Categories

More information

DOCTORAL THESIS (SUMMARY)

DOCTORAL THESIS (SUMMARY) Translation from Romanian UNIVERSITY OF MEDICINE AND PHARMACY CRAIOVA THE FACULTY OF MEDICINE DOCTORAL THESIS (SUMMARY) Scientific coordinator Prof. Dr. Laurentiu MOGOANTA PhD student, Dr. Madalin IONILA

More information

The Major Histocompatibility Complex (MHC)

The Major Histocompatibility Complex (MHC) The Major Histocompatibility Complex (MHC) An introduction to adaptive immune system before we discuss MHC B cells The main cells of adaptive immune system are: -B cells -T cells B cells: Recognize antigens

More information

AIDS - Knowledge and Dogma. Conditions for the Emergence and Decline of Scientific Theories Congress, July 16/ , Vienna, Austria

AIDS - Knowledge and Dogma. Conditions for the Emergence and Decline of Scientific Theories Congress, July 16/ , Vienna, Austria AIDS - Knowledge and Dogma Conditions for the Emergence and Decline of Scientific Theories Congress, July 16/17 2010, Vienna, Austria Reliability of PCR to detect genetic sequences from HIV Juan Manuel

More information

Phospho-AKT Sampler Kit

Phospho-AKT Sampler Kit Phospho-AKT Sampler Kit E 0 5 1 0 0 3 Kits Includes Cat. Quantity Application Reactivity Source Akt (Ab-473) Antibody E021054-1 50μg/50μl IHC, WB Human, Mouse, Rat Rabbit Akt (Phospho-Ser473) Antibody

More information

Clinicopathological and prognostic differences between mucinous gastric carcinoma and signet-ring cell carcinoma

Clinicopathological and prognostic differences between mucinous gastric carcinoma and signet-ring cell carcinoma Original Article Clinicopathological and prognostic differences between mucinous gastric carcinoma and signet-ring cell carcinoma Zhaode Bu, Zhixue Zheng, Ziyu Li, Xiaojiang Wu, Lianhai Zhang, Aiwen Wu,

More information

CONTRACTING ORGANIZATION: University of Southern California Los Angeles, CA 90033

CONTRACTING ORGANIZATION: University of Southern California Los Angeles, CA 90033 AD Award Number: W81XWH-07-01-0264 TITLE: Function of Klotho and is MicroRNA in Prostate Cancer and Aging PRINCIPAL INVESTIGATOR: Shao-Yao Ying, Ph.D. CONTRACTING ORGANIZATION: University of Southern California

More information

Protein Synthesis

Protein Synthesis Protein Synthesis 10.6-10.16 Objectives - To explain the central dogma - To understand the steps of transcription and translation in order to explain how our genes create proteins necessary for survival.

More information

Detachment of Transformed Cells

Detachment of Transformed Cells 9 1995 by Humana Press Inc. All rights of any nature whatsoever reserved. 0163-4992/95/261001-019/$7.80 Detachment of Transformed Cells Role of CD44 Variants CARLOS SANTOS, 1 KAREN CHANDLER, 2 STEPHEN

More information

The Role of CD164 in Metastatic Cancer Aaron M. Havens J. Wang, Y-X. Sun, G. Heresi, R.S. Taichman Mentor: Russell Taichman

The Role of CD164 in Metastatic Cancer Aaron M. Havens J. Wang, Y-X. Sun, G. Heresi, R.S. Taichman Mentor: Russell Taichman The Role of CD164 in Metastatic Cancer Aaron M. Havens J. Wang, Y-X. Sun, G. Heresi, R.S. Taichman Mentor: Russell Taichman The spread of tumors, a process called metastasis, is a dreaded complication

More information

HLA TYPING AND EXPRESSION: POTENTIAL MARKER FOR IDENTIFYING EARLY DYSPLASIA AND STRATIFYING THE RISK FOR IBD-CANCER

HLA TYPING AND EXPRESSION: POTENTIAL MARKER FOR IDENTIFYING EARLY DYSPLASIA AND STRATIFYING THE RISK FOR IBD-CANCER HLA TYPING AND EXPRESSION: POTENTIAL MARKER FOR IDENTIFYING EARLY DYSPLASIA AND STRATIFYING THE RISK FOR IBD-CANCER Megan Garrity, S. Breanndan Moore, M.D., William Sandborn, M.D., Vernon Pankratz, Ph.D.,

More information

Biochemistry of Cancer and Tumor Markers

Biochemistry of Cancer and Tumor Markers Biochemistry of Cancer and Tumor Markers The term cancer applies to a group of diseases in which cells grow abnormally and form a malignant tumor. It is a long term multistage genetic process. The first

More information

A Novel Chromatographic Method for Ep-CAM mrna Detection in Peripheral Blood and Bone Marrow of Patients with Metastatic Colorectal Cancer

A Novel Chromatographic Method for Ep-CAM mrna Detection in Peripheral Blood and Bone Marrow of Patients with Metastatic Colorectal Cancer A Novel Chromatographic Method for Ep-CAM mrna Detection in Peripheral Blood and Bone Marrow of Patients with Metastatic Colorectal Cancer CHARISIOS KARANIKIOTIS 1, IOANNIS SKIADAS 2, MARIA KARINA 3, STAVROULA

More information

Low levels of serum mir-99a is a predictor of poor prognosis in breast cancer

Low levels of serum mir-99a is a predictor of poor prognosis in breast cancer Low levels of serum mir-99a is a predictor of poor prognosis in breast cancer J. Li 1, Z.J. Song 2, Y.Y. Wang 1, Y. Yin 1, Y. Liu 1 and X. Nan 1 1 Tumor Research Department, Shaanxi Provincial Tumor Hospital,

More information

Quality in Control. ROS1 Analyte Control. Product Codes: HCL022, HCL023 and HCL024

Quality in Control. ROS1 Analyte Control. Product Codes: HCL022, HCL023 and HCL024 Quality in Control ROS1 Analyte Control Product Codes: HCL022, HCL023 and HCL024 Contents What is ROS1? 2 The Role of ROS1 in Cancer 3 ROS1 Assessment 3 ROS1 Analyte Control Product Details 4 ROS1 Analyte

More information

PROTEIN SYNTHESIS. It is known today that GENES direct the production of the proteins that determine the phonotypical characteristics of organisms.

PROTEIN SYNTHESIS. It is known today that GENES direct the production of the proteins that determine the phonotypical characteristics of organisms. PROTEIN SYNTHESIS It is known today that GENES direct the production of the proteins that determine the phonotypical characteristics of organisms.» GENES = a sequence of nucleotides in DNA that performs

More information

Colon Screening in 2014 Offering Patients a Choice. Clark A Harrison MD The Nevada Colon Cancer Partnership

Colon Screening in 2014 Offering Patients a Choice. Clark A Harrison MD The Nevada Colon Cancer Partnership Colon Screening in 2014 Offering Patients a Choice Clark A Harrison MD The Nevada Colon Cancer Partnership Objectives 1. Understand the incidence and mortality rates for CRC in the US. 2. Understand risk

More information

RD-100i OSNA the new generation of sentinel lymph node analysis in breast cancer

RD-100i OSNA the new generation of sentinel lymph node analysis in breast cancer RD-1i OSNA the new generation of sentinel lymph node analysis in breast cancer www.sysmex-europe.com RD-1i OSNA the new generation of sentinel lymph node analysis in breast cancer Sentinel node biopsy

More information

Prognosis after Treatment of Villous Adenomas

Prognosis after Treatment of Villous Adenomas Prognosis after Treatment of Villous Adenomas of the Colon and Rectum JOHN CHRISTIANSEN, M.D., PREBEN KIRKEGAARD, M.D., JYTTE IBSEN, M.D. With the existing evidence of neoplastic polyps of the colon and

More information

Chapter 4 Cellular Oncogenes ~ 4.6 -

Chapter 4 Cellular Oncogenes ~ 4.6 - Chapter 4 Cellular Oncogenes - 4.2 ~ 4.6 - Many retroviruses carrying oncogenes have been found in chickens and mice However, attempts undertaken during the 1970s to isolate viruses from most types of

More information

Supplementary Appendix

Supplementary Appendix Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Choi YL, Soda M, Yamashita Y, et al. EML4-ALK mutations in

More information

Cancer Fundamentals. Julie Randolph-Habecker, Ph.D. Director, Experimental Histopathology Shared Resource

Cancer Fundamentals. Julie Randolph-Habecker, Ph.D. Director, Experimental Histopathology Shared Resource Cancer Fundamentals Julie Randolph-Habecker, Ph.D. Director, Experimental Histopathology Shared Resource Cancer Overview Leading cause of death in US 1.2 million diagnosed each year More common after age

More information

Digestive System 7/15/2015. Outline Digestive System. Digestive System

Digestive System 7/15/2015. Outline Digestive System. Digestive System Digestive System Biology 105 Lecture 18 Chapter 15 Outline Digestive System I. Functions II. Layers of the GI tract III. Major parts: mouth, pharynx, esophagus, stomach, small intestine, large intestine,

More information

Computational Systems Biology: Biology X

Computational Systems Biology: Biology X Bud Mishra Room 1002, 715 Broadway, Courant Institute, NYU, New York, USA L#5:(October-18-2010) Cancer and Signals Outline 1 2 Outline 1 2 Cancer is a disease of malfunctioning cells. Cell Lineage: Adult

More information

SALSA MLPA probemix P315-B1 EGFR

SALSA MLPA probemix P315-B1 EGFR SALSA MLPA probemix P315-B1 EGFR Lot B1-0215 and B1-0112. As compared to the previous A1 version (lot 0208), two mutation-specific probes for the EGFR mutations L858R and T709M as well as one additional

More information

Shore Medical Center Site-Specific Study: Colorectal Cancer 2013

Shore Medical Center Site-Specific Study: Colorectal Cancer 2013 Shore Medical Center Site-Specific Study: Colorectal Cancer Shore Medical Center Site-Specific Study: Colorectal Cancer The following report is the result of a collaborative effort of four physician members

More information

Title Receptor, and Laminin/Collagen Rece. Citation Acta medica Nagasakiensia. 1993, 38

Title Receptor, and Laminin/Collagen Rece. Citation Acta medica Nagasakiensia. 1993, 38 NAOSITE: Nagasaki University's Ac Title Author(s) Immunohistochemical Investigation o Keratin, EMA, Laminin, Fibronectin, Receptor, and Laminin/Collagen Rece Senba, Masachika; Zhong, Xue-Yun; I Citation

More information

Corporate Medical Policy

Corporate Medical Policy Corporate Medical Policy Microarray-based Gene Expression Testing for Cancers of Unknown File Name: Origination: Last CAP Review: Next CAP Review: Last Review: microarray-based_gene_expression_testing_for_cancers_of_unknown_primary

More information

Update in Salivary Gland Pathology. Benjamin L. Witt University of Utah/ARUP Laboratories February 9, 2016

Update in Salivary Gland Pathology. Benjamin L. Witt University of Utah/ARUP Laboratories February 9, 2016 Update in Salivary Gland Pathology Benjamin L. Witt University of Utah/ARUP Laboratories February 9, 2016 Objectives Review the different appearances of a selection of salivary gland tumor types Establish

More information

Cancer genetics

Cancer genetics Cancer genetics General information about tumorogenesis. Cancer induced by viruses. The role of somatic mutations in cancer production. Oncogenes and Tumor Suppressor Genes (TSG). Hereditary cancer. 1

More information

MVST BOD & NST PART IB Thurs. 2 nd & Fri. 3 rd March 2017 Pathology Practical Class 23

MVST BOD & NST PART IB Thurs. 2 nd & Fri. 3 rd March 2017 Pathology Practical Class 23 MVST BOD & NST PART IB Thurs. 2 nd & Fri. 3 rd March 2017 Pathology Practical Class 23 Neoplasia I Neoplasia I: Benign and malignant neoplasms in glandular epithelium and mesenchyme 1.0. Aims 1. To understand

More information

Generation of antibody diversity October 18, Ram Savan

Generation of antibody diversity October 18, Ram Savan Generation of antibody diversity October 18, 2016 Ram Savan savanram@uw.edu 441 Lecture #10 Slide 1 of 30 Three lectures on antigen receptors Part 1 : Structural features of the BCR and TCR Janeway Chapter

More information

The Hallmarks of Cancer

The Hallmarks of Cancer The Hallmarks of Cancer Theresa L. Hodin, Ph.D. Clinical Research Services Theresa.Hodin@RoswellPark.org Hippocrates Cancer surgery, circa 1689 Cancer Surgery Today 1971: Nixon declares War on Cancer

More information

Expression of a Testis-Specific Form of TBP-Related Factor 2 (TRF2) mrna During Mouse Spermatogenesis

Expression of a Testis-Specific Form of TBP-Related Factor 2 (TRF2) mrna During Mouse Spermatogenesis Journal of Reproduction and Development, Vol. 49, No. 1, 2003 Research Note Expression of a Testis-Specific Form of TBP-Related Factor 2 (TRF2) mrna During Mouse Spermatogenesis Shin SUGIURA 1), Shin-ichi

More information