HER2 Gene Protein Assay Is Useful to Determine HER2 Status and Evaluate HER2 Heterogeneity in HER2 Equivocal Breast Cancer
|
|
- Avice Hutchinson
- 5 years ago
- Views:
Transcription
1 HER2 Gene Protein Assay Is Useful to Determine HER2 Status and Evaluate HER2 Heterogeneity in HER2 Equivocal Breast Cancer Yanjun Hou, MD, PhD, 1 Hiroaki Nitta, PhD, 2 and Zaibo Li, MD, PhD 1 From the 1 Department of Pathology, Wexner Medical Center at The Ohio State University, Columbus; and 2 Ventana Medical Systems, Tucson, AZ. Key Words: HER2 gene protein assay; Breast carcinoma; Immunohistochemistry; Fluorescence in situ hybridization; HER2 heterogeneity Am J Clin Pathol January 2017;147:89-95 DOI: /AJCP/AQW211 ABSTRACT Objectives: Approximately 15% of breast cancers show equivocal human epidermal growth factor receptor 2 (HER2) results on HER2 immunohistochemistry (IHC) and are reflexed for fluorescence in situ hybridization (FISH). However, some cases remain equivocal. In this study, we evaluated these double-equivocal cases by using a novel gene protein assay (GPA), which can simultaneously assess HER2 gene copy number and protein on a single slide using bright-field microscopy. Methods: GPA was performed on 42 HER2 IHC and FISH double-equivocal cases. Results: GPA was negative for amplification in 28 cases, equivocal in three cases, and positive in 11 cases. The GPA results showed excellent concordance with either repeat FISH using a chromosome 17 centromere probe or FISH using an alternative probe. Furthermore, HER2 heterogeneity was identified in three of 11 GPA-positive cases. Conclusions: HER2 GPA performs accurately and is very useful to determine HER2 status in HER2 IHC and FISH double-equivocal breast cancer cases and identify HER2 heterogeneity. Human epidermal growth factor receptor 2 (HER2; ERBB2) gene amplification and/or protein overexpression occur in up to 20% of breast cancers, and HER2 protein overexpression stimulates downstream signaling and then promotes cell proliferation and survival. 1-5 HER2 status is both a prognostic factor and a predictive factor for the effects of HER2-targeted therapies. The first humanized monoclonal antibody against HER2 protein, trastuzumab, has been demonstrated to be effective in HER2-positive primary and metastatic breast cancers Subsequently, other HER2 targeting agents such as pertuzumab (monoclonal antibody that prevents dimerization of HER2), adotrastuzumab emtansine (antibody drug conjugate), and lapatinib (small molecule inhibitor of epidermal growth factor receptor and HER2) have been developed and found to produce responses in patients with HER2-positive breast cancer. However, anti-her2 therapies are usually ineffective for HER2-negative breast cancers and can cause severe side effects to patients. Furthermore, anti-her2 therapies are costly. Therefore, it is necessary to accurately determine HER2 status in every single breast cancer case. HER2 status is usually assessed by immunohistochemistry (IHC) for HER2 protein overexpression or by fluorescence in situ hybridization (FISH) for HER2 gene amplification. Both methods were approved by the US Food and Drug Administration (FDA). IHC is used primarily and FISH is used as a reflex test on IHC 2þ cases by most laboratories in United States. FISH results have been accepted as a gold standard in the assessment of HER2 status. However, FISH uses dark-field fluorescence microscopy and lacks morphology details. Furthermore, the fluorescent American Society for Clinical Pathology, All rights reserved. For permissions, please journals.permissions@oup.com 89 Am J Clin Pathol 2017;147:
2 Hou et al /HER2GENE PROTEIN ASSAY signals fade over time; therefore, the slides cannot be stored for a long time. The bright-field in situ hybridization (BISH) methods, including chromogenic in situ hybridization, silver in situ hybridization, and dual in situ hybridization, have been developed to overcome some of the limitations of FISH However, sometimes it is difficult to differentiate tumor cells (low-grade tumor cells) from surrounding stromal cells or lymphocytes and recognize cell boundaries due to weak counterstaining. HER2 IHC and in situ hybridization (ISH) assays are used for the same purpose to select patients who benefit from anti-her2 therapies, but they detect biologically different targets, HER2 protein and HER2 gene, respectively. Each assay has its own advantages and disadvantages. The gene protein assay (GPA) described in this study merges HER2 IHC and BISH to assess HER2 status accurately in tumor cells by correlating with tissue morphology. A few pilot studies comparing GPA with IHC alone and FISH alone have shown concordance exceeding 90% by using tissue microarray (TMA) slides on both breast cancer and gastric cancer cases. 20,21 Our recent study had applied this method on HER2 IHC 2þ breast tumor whole sections and showed excellent concordance between GPA and FISH results. 22 The major discordant results of HER2 protein and HER2 gene statuses are caused by tumor heterogeneity, mainly detected in HER2-equivocal cases. Furthermore, the updated American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) HER2 testing guidelines have increased the number of HER2 double-equivocal cases (HER2 IHC 2þ and HER2 FISH equivocal) Therefore, our study aimed to apply this novel GPA method on the most challenging group of breast cancers (HER2 double-equivocal cases) to assess its clinical utility in this specific group of breast cancers. Materials and Methods Case Selection This study included whole tissue sections of 42 consecutive invasive breast cancer cases (32 core needle biopsy specimens, eight lumpectomy specimens, and two mastectomy specimens) with both equivocal HER2 IHC (IHC score 2þ) and initial HER2 FISH results on clinical testing at The Ohio State University Wexner Medical Center. In addition, five HER2 IHC 3þ/HER2 FISH-amplified and five HER2 IHC-negative/HER2 FISH nonamplified cases were also included in the study. The use of human materials was approved by the institutional review board at The Ohio State University. GPA The same tissue blocks with HER2 IHC and HER2 FISH performed were selected for GPA. GPA was performed on the BenchMark XT platform (Ventana Medical Systems, Tucson, AZ) according to the manufacturer s recommendation. The gene and protein detection combines PATHWAY anti-her2/neu (4B5) rabbit monoclonal primary antibody (Ventana Medical Systems) for IHC and the INFORM HER2 Dual ISH DNA probe cocktail (Ventana Medical Systems) for ISH on a single slide. As recommended, HER2 IHC was performed first using the iview DAB IHC Detection Kit (Ventana Medical Systems). Thereafter, hybridization was performed using a cocktail of the 2,4 dinitrophenyl (DNP) labeled HER2 probe and digoxigenin (DIG) labeled chromosome 17 centromere (CEN17) probe. The HER2 gene and CEN17 signals were detected using the ultraview Silver ISH DNP Detection Kit and ultraview Red ISH DIG Detection Kit (Ventana Medical Systems), respectively. The HER2 gene signals were detected prior to CEN17 detection. The slides were counterstained with Hematoxylin II (Ventana Medical Systems). Signal visualization was performed via light microscopy in which the HER2 gene appeared as discrete black signals and CEN17 as red signals in the nuclei, and the HER2 protein showed brown staining in the cell membranes. Representative GPA images are illustrated Image 1. FISH The FISH analysis with the CEN17 probe was performed at our institution using the dual-color Vysis FDAapproved PathVysion HER2 DNA Probe Kit (Abbott Molecular, Des Plaines, IL). The signals for the HER2 gene and CEN17 were visualized under a fluorescence microscope using appropriate filters. The average numbers of HER2 and CEN17 signals per cell were recorded for at least 50 cells, and the HER2/CEN17 ratio was calculated for each case. The results were interpreted by specialized molecular pathologists using the 2013 HER2 ASCO/CAP updated guidelines 26 and signed out by case pathologists specialized in breast pathology. The FISH with alternative probe (D17S122) was performed at The Mayo Clinic as a send-out test. The FISH results were reported back to our institution and entered into the record as an addendum. Interpretation GPA slides were interpreted for both HER2 IHC and HER2 ISH according to the 2013 HER2 ASCO/CAP guidelines. 26 For the ISH portion of the GPA, the staining results were enumerated by counting at least 50 nuclei by two 90 Am J Clin Pathol 2017;147:89-95 American Society for Clinical Pathology 90
3 A B C Image 1 Representative gene protein analysis (GPA) images. A, One case with GPA immunohistochemistry (IHC) negative and GPA in situ hybridization (ISH) negative results. B, One case with GPA-IHC positive and GPA-ISH amplified results. C, One case with GPA-IHC equivocal and GPA-ISH negative results. D, One case with GPA-IHC equivocal and GPA-ISH amplified results. pathologists (Y.H. and Z.L.). In cases with HER2 intratumoral heterogeneity, the areas with stronger IHC staining were selected for counting. Results GPA Results in Five HER2-Negative and HER21 Cases All five previously tested HER2-negative cases were again scored as 0 or 1þ on GPA-IHC and did not show increased HER2 signals per cell on GPA-ISH. Similarly, all five previously tested HER2-positive cases showed intense D complete membranous staining (3þ) on GPA-IHC and showed increased HER2 signals per cell on GPA-ISH. GPA Results in 42 HER2 Double-Equivocal Cases In 42 HER2 IHC and FISH double-equivocal cases, GPA-IHC was equivocal (2þ) for each case, but GPA-ISH was negative for amplification in 28 cases, equivocal in three cases, and positive in 11 cases. For 28 GPA-ISH negative cases, 12 had repeat FISH (CEN17) with 10 as negative and two as equivocal. Both cases with equivocal repeat FISH (CEN17) and negative GPA-ISH results were negative by FISH with alternative probes Figure 1. American Society for Clinical Pathology Am J Clin Pathol 2017;147:
4 Hou et al /HER2GENE PROTEIN ASSAY GPA Repeat FISH with CEN17 FISH with alternative probes +/ NA +/ + NA +/ + NA +/ NA +/ + NA +/ cells, all with more than 10% of tumor cells with HER2 signal >6/cell) Image 2B. Intracellular HER2 heterogeneity (defined by discordant HER2 gene amplification and protein expression in same cells) was also identified in those two cases with genetic heterogeneity Image 2C. In all three cases with heterogeneity, HER2 signals from GPA-ISH were greater than 6, while in the other eight GPA-positive cases, HER2 signals from GPA-ISH were less than 6 but with a ratio more than 2. Figure 1 Gene protein analysis (GPA) results and repeat fluorescence in situ hybridization (FISH) results with either CEN17 or alternative probe in 42 human epidermal growth factor receptor 2 (HER2) double-equivocal cases. NA, not applicable. For 11 GPA-ISH positive cases, eight cases had repeat FISH (CEN17) with three as positive and five as equivocal. FISH with alternative probes was performed in three cases with equivocal repeat FISH (CEN17) and positive GPA results and was positive in all three cases (Figure 1). For three GPA-equivocal cases, two cases had repeat FISH (CEN17), and both cases were negative (Figure 1). In the group of 28 GPA-negative cases, the HER2 signals from original FISH were greater than 4 per cell but less than 5, with a mean of All HER2 signals from GPA-ISH were less than 4 per cell. The mean HER2 signal from GPA-ISH was significantly less than the HER2 signal from original FISH (2.94 vs 4.44, P <.05), while the HER2/CEN17 ratio showed no difference between these two methods Table 1. In the group of 11 GPA-positive cases, the HER2 signals from original FISH were greater than 4 per cell but less than 6, with a mean of The HER2 signals from GPA- ISH ranged from 3.84 per cell to 12.56, including three cases with HER2 signals greater than 6 per cell and eight cases with HER2 signals between 4 and 6 but HER2/CEN17 ratios greater than 2. The mean HER2 signal from GPA-ISH was significantly greater than that from original FISH (5.77 vs 4.79, P <.05), while there was no significant difference in the HER2/CEN17 ratio between these two methods (Table 1). HER2 Heterogeneity Identified by GPA Furthermore, HER2 heterogeneity were identified in three of 11 GPA-positive cases, including one with regional heterogeneity (defined as the existence of amplificationnegative or amplification-equivocal patterns in different areas of the tumor) Image 2A and two with genetic heterogeneity (defined as the presence of scattered/small clustered tumor cells with HER2 amplification in 5%-50% of tumor Discussion To our knowledge, this is the first study to examine GPA s performance in breast carcinoma specimens with HER2 double-equivocal results (IHC 2þ and FISH equivocal) using the 2013 ASCO/CAP HER2 testing update guidelines. The GPA in the current study combines the anti- HER2 antibody for IHC and the HER2 Dual ISH DNA probes for ISH on a single slide. Limited studies had evaluated GPA in breast and gastric carcinomas. Nitta et al 20 and Hirschmann et al 21 performed GPA on TMA slides, and both studies found an excellent agreement between FISH and GPA-ISH (up to 95%). However, most of the cohort cases in both studies were either clearly negative or unequivocally positive cases. Our recent study examined GPA s performance on HER2 IHC 2þ cases and found an agreement of 82% with FISH results. 22 The 2013 updated ASCO/CAP HER2 testing guidelines have increased the number of HER2 double-equivocal cases (HER2 IHC 2þ and HER2 FISH equivocal). 26 In our current study, we performed GPA on the most challenging group of breast cancers (HER2 double-equivocal cases) using whole slides and found that GPA was able to recategorize 93% (39/42) of HER2 double-equivocal cases into an unequivocally negative or positive category with excellent concordance with either repeated FISH results using the CEN17 probe or an alternative probe. In the group of 28 GPA-negative cases, no intratumoral heterogeneity was identified, and all cases were reclassified as HER2 negative possibly because of more accurate counting by improved visualization. In the group of 11 GPA-positive cases, three cases were reclassified as HER2 positive because of intratumoral heterogeneity, and the other eight cases were reclassified as HER2 positive possibly because of more accurate counting by improved visualization. HER2 intratumoral heterogeneity has been reported in up to 40% of breast carcinomas and has gained more attention because of its impact on treatment decisions and effect The 2013 ASCO/CAP HER2 testing Update Committee recently recommended reporting any discrete population of amplified cells more than 10% of the total 92 Am J Clin Pathol 2017;147:89-95 American Society for Clinical Pathology 92
5 Table 1 HER2 Signal, CEN17 Signal, and Ratio in 28 GPA-Negative Cases and 11 GPA-Positive Cases GPA-Negative Cases (n ¼ 28), Mean (Range) GPA-Positive Cases (n ¼ 11), Mean (Range) Characteristic Original FISH GPA-ISH Original FISH GPA-ISH HER ( ) 2.94 ( ) 4.79 ( ) 5.77 ( ) CEN ( ) 2.08 ( ) 3.24 ( ) 2.12 ( ) Ratio 1.35 ( ) 1.43 ( ) 1.51 ( ) 2.79 ( ) CEN17, chromosome 17 centromere; FISH, fluorescence in situ hybridization; GPA, gene protein analysis; HER2, human epidermal growth factor receptor 2; ISH, in situ hybridization. A B C Image 2 Representative gene protein analysis images of cases with human epidermal growth factor receptor 2 heterogeneity. A, One case with regional heterogeneity. B, One case with genetic heterogeneity. The outlined areas show tumor cells with HER2 gene amplification and protein overexpression. C, One case with intracellular heterogeneity. The outlined areas show tumor cells with HER2 gene amplification but no protein overexpression. tumor cell population. 26 The 2013 Update Committee also suggested scanning the entire slide prior to counting and/or using an IHC HER2 test to define areas of potential amplification. 26 One of the main advantages of BISH assays, like IHC, is the ease of assessment of HER2 intratumoral heterogeneity. Therefore, a simultaneous assessment American Society for Clinical Pathology Am J Clin Pathol 2017;147:
6 Hou et al /HER2GENE PROTEIN ASSAY combining IHC and ISH on one slide would facilitate evaluation and enhance test efficiency, especially for cases with HER2 heterogeneity. Indeed, previous studies and our current study have found that HER2 intratumoral heterogeneity was appreciated much easier on GPA slides. In the current study, we identified that three of 11 HER2-postive cases on GPA had HER2 intratumoral heterogeneity, including one with regional heterogeneity and two with genetic and intracellular heterogeneity. Usually, regional heterogeneity can be highlighted by HER2 IHC, and then the potentially amplified areas can be circled for FISH. However, genetic heterogeneity is difficult to be assessed by FISH because HER2-amplified cells are intermixed with non HER2-amplified cells. However, GPA can overcome this difficulty because HER2 membranous staining is able to highlight the targeted cells for ISH assessment. In our institution, we perform both HER2 IHC and FISH at the initial biomarker evaluation. Occasionally, we have encountered breast carcinoma cases with negative HER2 IHC but positive HER2 FISH. This discordance between HER2 IHC and FISH may be explained by HER2 intracellular heterogeneity (HER2 gene amplification but no protein overexpression). As shown in one representative image (Image 2C), this intracellular heterogeneity is easily appreciated on the GPA slide. However, the intracellular heterogeneity will not be assessed by FISH. The GPA shows similar accuracy to the FISH method but a faster turnaround time (less than 24 hours) than FISH. Furthermore, GPA does not need a fluorescence microscope and does not require special training for interpretation. It is much easier to count HER2 signals and to differentiate tumor cells from surrounding stromal cells and lymphocytes on GPA slides because tumor cell boundaries are clearly noted by the IHC staining. Moreover, the IHC staining on GPA slides can be used to choose the interested area for counting. It is not uncommon that both HER2 IHC and FISH are performed simultaneously at initial breast biomarker assessment, like in our institution. GPA would be a perfect alternative in this setting because of its cost saving and faster turnaround time. Although many laboratories use HER2 IHC as a screening assay and reflex HER2 FISH for HER2 IHC 2þ cases, some outsource FISH to reference laboratories. GPA would be beneficial in such a setting where the IHC staining on GPA slides can be used to choose the interested area for counting. In summary, GPA performed accurately on the most challenging HER2 double-equivocal breast carcinoma cases and was able to recategorize up to 93% of HER2 doubleequivocal cases into an unequivocally negative or positive category with excellent concordance with repeated FISH results. Furthermore, HER2 intratumoral heterogeneity was easily assessed on GPA slides. Corresponding author: Zaibo Li, MD, PhD, Dept of Pathology, Wexner Medical Center at The Ohio State University, 410 W 10th Ave, Columbus, OH 43210;Zaibo.Li@osumc.edu. Disclosure: Y. Hou and Z. Li have no financial relationship to disclose. H. Nitta is an employee of Ventana Medical Systems. References 1. Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235: Press MF, Pike MC, Chazin VR, et al. Her-2/neu expression in node-negative breast cancer: direct tissue quantitation by computerized image analysis and association of overexpression with increased risk of recurrent disease. Cancer Res. 1993;53: Tandon AK, Clark GM, Chamness GC, et al. HER-2/neu oncogene protein and prognosis in breast cancer. J Clin Oncol. 1989;7: Lal P, Salazar PA, Hudis CA, et al. HER-2 testing in breast cancer using immunohistochemical analysis and fluorescence in situ hybridization: a single-institution experience of 2,279 cases and comparison of dual-color and single-color scoring. Am J Clin Pathol. 2004;121: Park JW, Neve RM, Szollosi J, et al. Unraveling the biologic and clinical complexities of HER2. Clin Breast Cancer. 2008;8: Ross JS, Slodkowska EA, Symmans WF, et al. The HER-2 receptor and breast cancer: ten years of targeted anti-her-2 therapy and personalized medicine. Oncologist. 2009;14: Olson EM. Maximizing human epidermal growth factor receptor 2 inhibition: a new oncologic paradigm in the era of targeted therapy. J Clin Oncol. 2012;30: Cobleigh MA, Vogel CL, Tripathy D, et al. Multinational study of the efficacy and safety of humanized anti-her2 monoclonal antibody in women who have HER2- overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol. 1999;17: Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344: Seidman AD, Fornier MN, Esteva FJ, et al. Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification. J Clin Oncol. 2001;19: Vogel CL, Cobleigh MA, Tripathy D, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2002;20: Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353: Am J Clin Pathol 2017;147:89-95 American Society for Clinical Pathology 94
7 13. Viani GA, Afonso SL, Stefano EJ, et al. Adjuvant trastuzumab in the treatment of her-2 positive early breast cancer: a meta-analysis of published randomized trials. BMC Cancer. 2007;7: Isola J, Tanner M, Forsyth A, et al. Interlaboratory comparison of HER-2 oncogene amplification as detected by chromogenic and fluorescence in situ hybridization. Clin Cancer Res. 2004;10: Pedersen M, Rasmussen BB. The correlation between dualcolor chromogenic in situ hybridization and fluorescence in situ hybridization in assessing HER2 gene amplification in breast cancer. Diagn Mol Pathol. 2009;18: Kato N, Itoh H, Serizawa A, et al. Evaluation of HER2 gene amplification in invasive breast cancer using a dual-color chromogenic in situ hybridization (dual CISH). Pathol Int. 2010;60: Papouchado BG, Myles J, Lloyd RV, et al. Silver in situ hybridization (SISH) for determination of HER2 gene status in breast carcinoma: comparison with FISH and assessment of interobserver reproducibility. Am J Surg Pathol. 2010;34: Koh YW, Lee HJ, Lee JW, et al. Dual-color silver-enhanced in situ hybridization for assessing HER2 gene amplification in breast cancer. Mod Pathol. 2011;24: Park K, Han S, Kim JY, et al. Silver-enhanced in situ hybridization as an alternative to fluorescence in situ hybridization for assaying HER2 amplification in clinical breast cancer. J Breast Cancer. 2011;14: Nitta H, Kelly BD, Padilla M, et al. A gene-protein assay for human epidermal growth factor receptor 2 (HER2): brightfield tricolor visualization of HER2 protein, the HER2 gene, and chromosome 17 centromere (CEN17) in formalin-fixed, paraffin-embedded breast cancer tissue sections. Diagn Pathol. 2012;7: Hirschmann A, Lamb TA, Marchal G, et al. Simultaneous analysis of HER2 gene and protein on a single slide facilitates HER2 testing of breast and gastric carcinomas. Am J Clin Pathol. 2012;138: Li Z, Dabbs DJ, Cooper KL, Bhargava R. Dual HER2 gene protein assay: focused study of breast cancers with 2þ immunohistochemical expression. Am J Clin Pathol. 2015;143: Bethune GC, Veldhuijzen van Zanten D, MacIntosh RF, et al. Impact of the 2013 American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing of invasive breast carcinoma: a focus on tumours assessed as 0 equivocal 0 for HER2 gene amplification by fluorescence in-situ hybridization. Histopathology. 2015;67: Lim TH, Lim AS, Thike AA, et al. Implications of the updated 2013 American Society of Clinical Oncology/ College of American Pathologists Guideline Recommendations on human epidermal growth factor receptor 2 gene testing using immunohistochemistry and fluorescence in situ hybridization for breast cancer. Arch Pathol Lab Med. 2016;140: Varga Z, Noske A. Impact of modified 2013 ASCO/CAP guidelines on HER2 testing in breast cancer: one year experience. PLoS One. 2015;10:e Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. JClinOncol. 2013;31: Ohlschlegel C, Zahel K, Kradolfer D, et al. HER2 genetic heterogeneity in breast carcinoma. J Clin Pathol. 2011;64: Murthy SS, Sandhya DG, Ahmed F, et al. Assessment of HER2/Neu status by fluorescence in situ hybridization in immunohistochemistry-equivocal cases of invasive ductal carcinoma and aberrant signal patterns: a study at a tertiary cancer center. Indian J Pathol Microbiol. 2011;54: Chang MC, Malowany JI, Mazurkiewicz J, et al. Genetic heterogeneity in HER2/neu testing by fluorescence in situ hybridization: a study of 2,522 cases. Mod Pathol. 2012;25: Allison KH, Dintzis SM, Schmidt RA. Frequency of HER2 heterogeneity by fluorescence in situ hybridization according to CAP expert panel recommendations: time for a new look at how to report heterogeneity. Am J Clin Pathol. 2011;136: Bartlett AI, Starcyznski J, Robson T, et al. Heterogeneous HER2 gene amplification: impact on patient outcome and a clinically relevant definition. Am J Clin Pathol. 2011;136: Seol H, Lee HJ, Choi Y, et al. Intratumoral heterogeneity of HER2 gene amplification in breast cancer: its clinicopathological significance. Mod Pathol. 2012;25: American Society for Clinical Pathology Am J Clin Pathol 2017;147:
Priti Lal, MD, 1 Paulo A. Salazar, 1 Clifford A. Hudis, MD, 2 Marc Ladanyi, MD, 1 and Beiyun Chen, MD, PhD 1. Abstract
Anatomic Pathology / DUAL- VS SINGLE-COLOR SCORING IN IMMUNOHISTOCHEMICAL AND FISH HER-2 TESTING HER-2 Testing in Breast Cancer Using Immunohistochemical Analysis and Fluorescence In Situ Hybridization
More informationJournal of Breast Cancer
ORIGINAL ARTICLE Journal of Breast Cancer J Breast Cancer 2009 December; 12(4): 235-40 DOI: 10.4048/jbc.2009.12.4.235 Comparison of Silver-Enhanced in situ Hybridization and Fluorescence in situ Hybridization
More informationKristen E. Muller, DO, Jonathan D. Marotti, MD, Vincent A. Memoli, MD, Wendy A. Wells, MD, and Laura J. Tafe, MD
AJCP / Original Article Impact of the 2013 ASCO/CAP HER2 Guideline Updates at an Academic Medical Center That Performs Primary HER2 FISH Testing Increase in Equivocal Results and Utility of Reflex Immunohistochemistry
More informationNitta et al. Diagnostic Pathology 2012, 7:60
Nitta et al. Diagnostic Pathology 2012, 7:60 METHODOLOGY Open Access A gene-protein assay for human epidermal growth factor receptor 2 (HER2): brightfield tricolor visualization of HER2 protein, the HER2
More informationCME/SAM ABSTRACT. AJCP / Original Article
Clinicopathologic Significance of the Intratumoral Heterogeneity of HER2 Gene Amplification in HER2- Positive Breast Cancer Patients Treated With Adjuvant Trastuzumab Hee Jin Lee, MD, PhD, 1 Joo Young
More informationDr. dr. Primariadewi R, SpPA(K)
Curriculum Vitae Dr. dr. Primariadewi R, SpPA(K) Education : Medical Doctor from UKRIDA Doctoral Degree from Faculty of Medicine University of Indonesia Pathologist Specialist and Consultant from Faculty
More informationMEDICAL POLICY. Proprietary Information of YourCare Health Plan
MEDICAL POLICY SUBJECT: HER-2 TESTING IN INVASIVE BREAST OR PAGE: 1 OF: 7 If the member's subscriber contract excludes coverage for a specific service it is not covered under that contract. In such cases,
More informationHER2 Testing of Multifocal Invasive Breast Carcinoma. Gillian C. Bethune, MD, J. Brendan Mullen, MD, and Martin C. Chang, MD, PhD
HER2 Testing of Multifocal Invasive Breast Carcinoma How Many Blocks Are Enough? Gillian C. Bethune, MD, J. Brendan Mullen, MD, and Martin C. Chang, MD, PhD From the Department of Pathology and Laboratory
More informationHER2/neu Evaluation of Breast Cancer in 2019
HER2/neu Evaluation of Breast Cancer in 2019 A.A. Sahin, M.D. Professor of Pathology and Translation Molecular Pathology Section Chief of Breast Pathology ERBB2 (HER2) Background 185-kDa membrane protein
More informationReview Article The assessment of HER2 status in breast cancer: the past, the present, and the future
Pathology International 2016; 66: 313 324 doi:10.1111/pin.12407 Review Article The assessment of HER2 status in breast cancer: the past, the present, and the future Hiroaki Nitta, 1 Brian D. Kelly, 2 Craig
More informationReviewer's report. Version: 1 Date: 24 May Reviewer: Cathy Moelans. Reviewer's report:
Reviewer's report Title: Validation of HER2 testing with core needle biopsy specimens from primary breast cancers in terms of interobserver reproducibility and concordance with surgically resected specimens
More informationMEDICAL POLICY. Proprietary Information of Excellus Health Plan, Inc. A nonprofit independent licensee of the BlueCross BlueShield Association
MEDICAL POLICY SUBJECT: HER-2 TESTING IN INVASIVE BREAST OR PAGE: 1 OF: 7 If a product excludes coverage for a service, it is not covered, and medical policy criteria do not apply. If a commercial product,
More informationWhat is HER2 positive breast cancer in 2018? Updated ASCO-CAP guidelines. Giuseppe Viale University of Milan European Institute of Oncology
What is HER2 positive breast cancer in 2018? Updated ASCO-CAP guidelines Giuseppe Viale University of Milan European Institute of Oncology Mission accomplished! First alarming results Breast Intergroup
More informationVersion 2 of these Guidelines were drafted in response to published updated ASCO/CAP HER2 test Guideline Recommendations-
Introduction: These guidelines represent systematically developed statements to assist in the provision of quality assured HER2 testing in breast and gastric/ gastro-oesophageal carcinoma. They are based
More informationHER2/neu Amplification in Breast Cancer Stratification by Tumor Type and Grade
Anatomic Pathology / HER2/NEU AMPLIFICATION IN BREAST CANCER HER2/neu Amplification in Breast Cancer Stratification by Tumor Type and Grade Elise R. Hoff, MD, Raymond R. Tubbs, DO, Jonathan L. Myles, MD,
More informationCME/SAM. HER2 Heterogeneity Affects Trastuzumab Responses and Survival in Patients With HER2-Positive Metastatic Breast Cancer
AJCP / Original Article HER2 Heterogeneity Affects Trastuzumab Responses and Survival in Patients With HER2-Positive Metastatic Breast Cancer Hee Jin Lee, MD,,7 An Na Seo, MD, Eun Joo Kim, Min Hye Jang,
More informationHER2 ISH (BRISH or FISH)
Assessment Run H14 2018 HER2 ISH (BRISH or FISH) Material Table 1. Content of the multi-block used for the NordiQC HER2 ISH assessment, run H14 HER2 IHC* IHC score Dual - SISH** FISH*** FISH*** HER2/chr17
More informationJournal of Breast Cancer
Journal of Breast Cancer ORIGINAL ARTICLE J Breast Cancer 2011 December; 14(4): 276-282 Silver-Enhanced In Situ Hybridization as an Alternative to Fluorescence In Situ Hybridization for Assaying HER2 Amplification
More informationHER2 CISH pharmdx TM Kit Interpretation Guide Breast Cancer
P A T H O L O G Y HER2 CISH pharmdx TM Kit Interpretation Guide Breast Cancer FROM CERTAINTY COMES TRUST For in vitro diagnostic use HER2 CISH pharmdx Kit HER2 CISH pharmdx Kit is intended for dual-color
More informationImmunohistochemical (IHC) HER-2/neu and Fluorescent- In Situ Hybridization (FISH) Gene Amplification of Breast Cancer in Indian Women
Comparison of IHC and FISH for HER-2/neu Status of Breast Cancer in Indian Women RESEARCH COMMUNICATION Immunohistochemical (IHC) HER-2/neu and Fluorescent- In Situ Hybridization (FISH) Gene Amplification
More informationGenetic heterogeneity in HER2/neu testing by fluorescence in situ hybridization: a study of 2522 cases
Modern Pathology () 5, 683 688 & USCAP, Inc. All rights reserved 893-395/ $3. 683 Genetic heterogeneity in HER/neu testing by fluorescence in situ hybridization: a study of 5 cases Martin C Chang,,3, Janet
More informationCME/SAM. Abstract. Anatomic Pathology / HER2/neu Results in Breast Cancer
Anatomic Pathology / HER2/neu Results in Breast Cancer Effect of Ischemic Time, Fixation Time, and Fixative Type on HER2/neu Immunohistochemical and Fluorescence In Situ Hybridization Results in Breast
More informationOriginal article. A novel gene-protein assay for evaluating HER2 status in gastric cancer: simultaneous
Original article A novel gene-protein assay for evaluating HER2 status in gastric cancer: simultaneous analyses of HER2 protein over-expression and gene-amplification reveal intratumoral heterogeneity
More informationHER2 Status and Its Heterogeneity in Gastric Carcinoma of Vietnamese Patient
Journal of Pathology and Translational Medicine 2017; 51: 396-402 ORIGINAL ARTICLE HER2 Status and Its Heterogeneity in Gastric Carcinoma of Vietnamese Patient Dang Anh Thu Phan Vu Thien Nguyen Thi Ngoc
More informationHER2 status assessment in breast cancer. Marc van de Vijver Academic Medical Centre (AMC), Amsterdam
HER2 status assessment in breast cancer Marc van de Vijver Academic Medical Centre (AMC), Amsterdam 13e Bossche Mamma Congres 17 th June 2015 Modern cancer therapies are based on sophisticated molecular
More informationT he HER2/neu type 1 tyrosine kinase growth factor
710 ORIGINAL ARTICLE HER2 amplification status in breast cancer: a comparison between immunohistochemical staining and fluorescence in situ hybridisation using manual and automated quantitative image analysis
More informationLow ER+ Breast Cancer. Is This a Distinct Group? Nika C. Gloyeske, MD, David J. Dabbs, MD, and Rohit Bhargava, MD ABSTRACT
Low ER+ Breast Cancer Is This a Distinct Group? Nika C. Gloyeske, MD, David J. Dabbs, MD, and Rohit Bhargava, MD From the Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, PA.
More informationWelcome! HER2 TESTING DIAGNOSTIC ACCURACY 4/11/2016
HER2 TESTING DIAGNOSTIC ACCURACY Can t We Finally Get It Right? Allen M. Gown, M.D. Medical Director and Chief Pathologist PhenoPath Laboratories Seattle, Washington Clinical Professor of Pathology University
More informationComparison of Immunohistochemical and Fluorescence In Situ Hybridization Assessment of HER-2 Status in Routine Practice
Anatomic Pathology / ASSESSMENT OF HER-2 STATUS Comparison of Immunohistochemical and Fluorescence In Situ Hybridization Assessment of HER-2 Status in Routine Practice Michelle Dolan, MD, 1 and Dale Snover,
More informationDetermination of HER2 Amplification by In Situ Hybridization. When Should Chromosome 17 Also Be Determined?
Anatomic Pathology / FISH f o r HER2: Wh e n to Use Ch r o m o s o m e 17 Determination of HER2 Amplification by In Situ Hybridization When Should Chromosome 17 Also Be Determined? John M.S. Bartlett,
More informationQuantitative Image Analysis of HER2 Immunohistochemistry for Breast Cancer
Quantitative Image Analysis of HER2 Immunohistochemistry for Breast Cancer Guideline from the College of American Pathologists Early Online Release Publication: Archives of Pathology & Laboratory Medicine
More informationFAQs for UK Pathology Departments
FAQs for UK Pathology Departments This is an educational piece written for Healthcare Professionals FAQs for UK Pathology Departments If you would like to discuss any of the listed FAQs further, or have
More informationCANCER. Clinical Validation of Breast Cancer Predictive Markers
Clinical Validation of Breast Cancer Predictive Markers David Hicks, MD Loralee McMahon, MS, HTL(ASCP) CANCER The human body is composed of billions of highly regulated cells Cancer cells no longer respond
More informationMolecular Probes Introducing 14 new probes
Molecular Probes Introducing 14 new probes Gene and Chromosome Probes Dual Colour ISH INFORM HER2 Dual ISH DNA Probe Cocktail Assay Product Part Number INFORM HER2 Dual ISH DNA Probe Cocktail 800-4422
More informationHER2 FISH pharmdx TM Interpretation Guide - Breast Cancer
P A T H O L O G Y HER2 FISH pharmdx TM Interpretation Guide - Breast Cancer For In Vitro Diagnostic Use FDA approved as an aid in the assessment of patients for whom Herceptin TM (trastuzumab) treatment
More informationThree Hours Thirty Minutes
INTERPRETATION HER2 IQFISH pharmdx TM Interpretation Guide Three Hours Thirty Minutes it s about time Breast carcinoma (FFPE) stained with HER2 IQFISH pharmdx Gastric cancer (FFPE) stained with HER2 IQFISH
More informationIntratumoral Heterogeneity in Breast Cancer: A Case Report and Molecular Discussion
Original Case Report Article Middle East Journal of Cancer; July October 20152018; 6(3): 9(4): 339-343 Intratumoral Heterogeneity in Breast Cancer: A Case Report and Molecular Discussion Akbar Safaei,
More informationCME/SAM. Abstract. Anatomic Pathology / Image Analysis of HER2 Immunostaining
Anatomic Pathology / Image Analysis of HER2 Immunostaining Image Analysis of HER2 Immunohistochemical Staining Reproducibility and Concordance With Fluorescence In Situ Hybridization of a Laboratory-Validated
More informationHER2 status in breast cancer: experience of a Spanish National Reference Centre
Clin Transl Oncol (2011) 13:000-000 DOI RESEARCH ARTICLES HER2 status in breast cancer: experience of a Spanish National Reference Centre Marta Cuadros Carlos Cano Francisco Javier López Paloma Talavera
More information2017 OPTIONS FOR INDIVIDUAL MEASURES: REGISTRY ONLY. MEASURE TYPE: Process
Measure #449 (NQF 1857): HER2 Negative or Undocumented Breast Cancer Patients Spared Treatment with HER2-Targeted Therapies National Quality Strategy Domain: Efficiency and Cost Reduction 2017 OPTIONS
More informationEnhanced Accuracy and Reliability of HER-2/neu Immunohistochemical Scoring Using Digital Microscopy
Anatomic Pathology / HER-2 IMMUNOHISTOCHEMICAL SCORING RELIABILITY Enhanced Accuracy and Reliability of HER-2/neu Immunohistochemical Scoring Using Digital Microscopy Kenneth Bloom, MD, 1 and Douglas Harrington,
More informationDepartment of Pathology, Loyola University Medical Center, Maywood, IL 60153, USA 2
Hindawi Publishing Corporation Pathology Research International Volume 2012, Article ID 947041, 7 pages doi:10.1155/2012/947041 Clinical Study The Effect of Cold Ischemia Time and/or Formalin Fixation
More informationHER2+ Breast Cancer Review of Biologic Relevance and Optimal Use of Diagnostic Tools
Anatomic Pathology / HER2: BIOLOGIC RELEVANCE AND DIAGNOSIS HER2+ Breast Cancer Review of Biologic Relevance and Optimal Use of Diagnostic Tools David G. Hicks, MD, 1 and Swati Kulkarni, MD 2 Key Words:
More informationProduct Introduction
Product Introduction Product Codes: HCL026, HCL027 and HCL028 Contents Introduction to HER2 2 HER2 immunohistochemistry 3 Cell lines as controls 5 HER2 Analyte Control DR IHC 7 HER2 Analyte Control DR
More informationData Supplement 1: 2013 Update Rationale and Background Information
Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology /College of American Pathologists Clinical Practice Guideline Update (edited
More informationConsiderable advances in the therapy of breast cancer
HER-2/neu Status in Breast Cancer Metastases to the Central Nervous System Kelly C. Lear-Kaul, MD; Hye-Ryoung Yoon, MD; Bette K. Kleinschmidt-DeMasters, MD; Loris McGavran, PhD; Meenakshi Singh, MD Context.
More informationTemplate for Reporting Results of Biomarker Testing of Specimens From Patients With Carcinoma of the Breast
Template for Reporting Results of Biomarker Testing of Specimens From Patients With Carcinoma of the Breast Version: Template Posting Date: January 2018 Includes requirements from the 2017 CAP Accreditation
More informationImportance of confirming HER2 overexpression of recurrence lesion in breast cancer patients
Breast Cancer (2013) 20:336 341 DOI 10.1007/s12282-012-0341-6 ORIGINAL ARTICLE Importance of confirming HER2 overexpression of recurrence lesion in breast cancer patients Rikiya Nakamura Naohito Yamamoto
More informationAssessment Run B HER2 IHC
Assessment Run B24 2017 HER2 IHC Material The slide to be stained for HER2 comprised the following 5 materials: IHC: HER2 Score* (0, 1+, 2+, 3+) FISH: HER2 gene/chr 17 ratio** 1. Breast carcinoma, no.
More informationGuideline. Associated Documents ASCO CAP 2018 GUIDELINES and SUPPLEMENTS -
Guideline Subject: ASCO CAP 2018 HER2 Testing for Breast Cancer Guidelines - Recommendations for Practice in Australasia Approval Date: December 2018 Review Date: December 2022 Review By: HER2 testing
More informationSurgical Pathology Lab of the Future. Thomas M. Grogan, M.D. Professor of Pathology, University of Arizona Founder, Ventana Medical Systems, Inc.
Surgical Pathology Lab of the Future Thomas M. Grogan, M.D. Professor of Pathology, University of Arizona Founder, Ventana Medical Systems, Inc. 28 April 2010 Objective Demonstrate how the next generation
More informationComparison of in situ hybridization methods for the assessment of HER-2/neu gene amplification status in breast cancer using a tissue microarray
reports of practical oncology and radiotherapy 1 7 ( 2 0 1 2 ) 44 49 Available online at www.sciencedirect.com jo u r n al hom epage: http://www.elsevier.com/locate/rpor Original article Comparison of
More informationEditorial New guidelines for HER2 pathological diagnostics in gastric cancer
bs_bs_banner Pathology International 2016; 66: 57 62 doi:10.1111/pin.12390 Editorial New guidelines for HER2 pathological diagnostics in gastric cancer Ryo Wada, 1 Kenichi Hirabayashi, 2 Nobuyuki Ohike
More informationUniversity of Groningen
University of Groningen Validation of the 4B5 rabbit monoclonal antibody in determining Her2/neu status in breast cancer van der Vegt, Bert; de Bock, Gertruida H; Bart, Jos; Zwartjes, N.G.; Wesseling,
More informationDroplet digital PCR using HER2/EIF2C1 ratio for detection of HER2 amplification in breast cancer tissues
https://doi.org/10.1007/s12032-018-1210-8 ORIGINAL PAPER Droplet digital PCR using HER2/EIF2C1 ratio for detection of HER2 amplification in breast cancer tissues Anchalee Tantiwetrueangdet 1 Ravat Panvichian
More informationExpression of human epidermal growth factor receptor 2 in primary and paired parenchymal recurrent and/or metastatic sites of gastric cancer
MOLECULAR AND CLINICAL ONCOLOGY 2: 751-755 Expression of human epidermal growth factor receptor 2 in primary and paired parenchymal recurrent and/or metastatic sites of gastric cancer RYOSUKE SHIBATA 1,
More information2019 COLLECTION TYPE: MIPS CLINICAL QUALITY MEASURES (CQMS) MEASURE TYPE: Process High Priority
Quality ID #449 (NQF 1857): HER2 Negative or Undocumented Breast Cancer Patients Spared Treatment with HER2-Targeted Therapies National Quality Strategy Domain: Efficiency and Cost Reduction Meaningful
More information# Best Practices for IHC Detection and Interpretation of ER, PR, and HER2 Protein Overexpression in Breast Cancer
#1034 - Best Practices for IHC Detection and Interpretation of ER, PR, and HER2 Protein Overexpression in Breast Cancer Richard W. Cartun, MS, PhD Andrew Ricci, Jr, MD Department of Pathology Hartford
More informationAssessment of Breast Cancer with Borderline HER2 Status Using MIP Microarray
Assessment of Breast Cancer with Borderline HER2 Status Using MIP Microarray Hui Chen, Aysegul A Sahin, Xinyan Lu, Lei Huo, Rajesh R Singh, Ronald Abraham, Shumaila Virani, Bal Mukund Mishra, Russell Broaddus,
More informationHuman epidermal growth factor receptor 2 (HER2)
Utility of Alternate, Noncentromeric Chromosome 17 Reference Probe for Human Epidermal Growth Factor Receptor Fluorescence In Situ Hybridization Testing in Breast Cancer Cases Trupti Pai, MD; Tanuja Shet,
More informationBreast Cancer Interpretation Guide
Breast Cancer Interpretation Guide UCT D O R P NEW ERBB2/ C E P S ht e ZytoLig lor Prob o C l a u 2D D17S12 ng to the i d r o c c a ting for re-tes idelines 2013 ASCO Gu Breast Cancer Interpretation Guide
More informationOptimal algorithm for HER2 testing
Optimal algorithm for HER2 testing The revised definition of IHC 2+ (equivocal) is invasive breast cancer with Weak to moderate complete membrane staining observed in >10% of tumor cells. (see Figure 1
More informationEARLY ONLINE RELEASE
EARLY ONLINE RELEASE Note: This article was posted on the Archives Web site as an Early Online Release. Early Online Release articles have been peer reviewed, copyedited, and reviewed by the authors. Additional
More informationPrediction of HER2 gene status in Her2 2 þ invasive breast cancer: a study of 108 cases comparing ASCO/CAP and FDA recommendations
& 2009 USCAP, Inc All rights reserved 0893-3952/09 $32.00 www.modernpathology.org Prediction of HER2 gene status in Her2 2 þ invasive breast cancer: a study of 108 cases comparing ASCO/CAP and FDA recommendations
More informationNIH Public Access Author Manuscript Cancer Epidemiol Biomarkers Prev. Author manuscript; available in PMC 2011 January 1.
NIH Public Access Author Manuscript Published in final edited form as: Cancer Epidemiol Biomarkers Prev. 2010 January ; 19(1): 144 147. doi:10.1158/1055-9965.epi-09-0807. Feasibility Study for Collection
More informationApplications of IHC. Determination of the primary site in metastatic tumors of unknown origin
Applications of IHC Determination of the primary site in metastatic tumors of unknown origin Classification of tumors that appear 'undifferentiated' by standard light microscopy Precise classification
More informationFirst released in 2007 and updated in 2013, the recommendations
Special Article Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update Antonio
More informationAssessment Run B HER2 IHC
Assessment Run B26 208 HER2 IHC Material The slide to be stained for HER2 comprised the following 5 materials: IHC: HER2 Score* (0, +, 2+, 3+) FISH: HER2 gene/chr 7 ratio**. Breast carcinoma, no. 2+..3
More informationComparison of Fluorescence and Chromogenic In Situ Hybridization for Detection of HER-2/neu Oncogene in Breast Cancer
Anatomic Pathology / HER-2 DETECTION BY CISH IN BREAST CANCER Comparison of Fluorescence and Chromogenic In Situ Hybridization for Detection of HER-2/neu Oncogene in Breast Cancer Deepali Gupta, MD, 1
More informationCOMPUTER-AIDED HER-2/neu EVALUATION IN EXTERNAL QUALITY ASSURANCE (EQA) OF BREAST CANCER SCREENING PROGRAMME
COMPUTER-AIDED HER-2/neu EVALUATION IN EXTERNAL QUALITY ASSURANCE (EQA) OF BREAST CANCER SCREENING PROGRAMME Maria Lunardi MD Anatomic Pathology Fracastoro Hospital San Bonifacio, Verona -Italy HER2-neu
More informationA Study Comparing Conventional Brightfield Microscopy, Image Analysis-Assisted Microscopy, and Interobserver Variation
Effects of the Change in Cutoff Values for Human Epidermal Growth Factor Receptor 2 Status by Immunohistochemistry and Fluorescence In Situ Hybridization A Study Comparing Conventional Brightfield Microscopy,
More information저작권법에따른이용자의권리는위의내용에의하여영향을받지않습니다.
저작자표시 - 비영리 - 동일조건변경허락 2.0 대한민국 이용자는아래의조건을따르는경우에한하여자유롭게 이저작물을복제, 배포, 전송, 전시, 공연및방송할수있습니다. 이차적저작물을작성할수있습니다. 다음과같은조건을따라야합니다 : 저작자표시. 귀하는원저작자를표시하여야합니다. 비영리. 귀하는이저작물을영리목적으로이용할수없습니다. 동일조건변경허락. 귀하가이저작물을개작, 변형또는가공했을경우에는,
More informationAssessment Run B HER-2 IHC. HER-2/chr17 ratio**
Assessment Run B2 20 HER-2 IHC Material The slide to be stained for HER-2 comprised the following 5 tissues: IHC HER-2 Score* (0, +, 2+,3+) FISH HER-2/chr7 ratio**. Breast ductal carcinoma 0..3 2. Breast
More informationTaxotere * and carboplatin plus Herceptin (trastuzumab) (TCH): the first approved non-anthracycline Herceptin-containing regimen 1
Important data from BCIRG 006 Taxotere * and carboplatin plus Herceptin (trastuzumab) (TCH): the first approved non-anthracycline Herceptin-containing regimen 1 in the adjuvant treatment of HER2+ breast
More informationControversies in HER2 Oncogene Testing: What Constitutes a True Positive Result in Patients With Breast Cancer?
Controversies in HER2 Oncogene Testing: What Constitutes a True Positive Result in Patients With Breast Cancer? Michael F. Press, MD, PhD; Yanling Ma, MD; Susan Groshen, PhD; Guido Sauter, MD, PhD; and
More informationDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
& 2005 USCAP, Inc All rights reserved 0893-3952/05 $30.00 www.modernpathology.org Reliability of chromogenic in situ hybridization for detecting HER-2 gene status in breast cancer: comparison with fluorescence
More informationIT S ABOUT TIME. IQFISH pharmdx Interpretation Guide THREEHOURSTHIRTYMINUTES. HER2 IQFISH pharmdxtm. TOP2A IQFISH pharmdxtm
I N T E R P R E TAT I O N IQFISH pharmdx Interpretation Guide TM HER2 IQFISH pharmdxtm TOP2A IQFISH pharmdxtm Breast carcinoma (FFPE) stained with HER2 IQFISH pharmdx Breast carcinoma (FFPE) stained with
More informationAssessing the Potential Cost-Effectiveness of Retesting IHC0, IHC11, or FISH-Negative Early Stage Breast Cancer Patients for HER2 Status
Assessing the Potential Cost-Effectiveness of Retesting IHC0, IHC11, or FISH-Negative Early Stage Breast Cancer Patients for HER2 Status Louis P. Garrison Jr., PhD 1,2 ; Deepa Lalla, PhD 3 ; Melissa Brammer,
More informationOn May 4 and 5, 2002, the College of American Pathologists
College of American Pathologists Conference Conference Summary, Strategic Science Symposium Her-2/neu Testing of Breast Cancer Patients in Clinical Practice Richard J. Zarbo, MD, DMD; M. Elizabeth H. Hammond,
More informationJ Clin Oncol 26: by American Society of Clinical Oncology INTRODUCTION
VOLUME 26 NUMBER 30 OCTOBER 20 2008 JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T Polysomy 17 in Breast Cancer: Clinicopathologic Significance and Impact on HER-2 Testing Isabelle Vanden Bempt,
More informationINTRODUCTION. Aravind Barathi Asogan 1, MBBS, MRCSEd, Ga Sze Hong 2, FRCS, FAMS, Subash Kumar Arni Prabhakaran 1, MBBS, FRCS
Singapore Med J 2017; 58(3): 145-149 doi: 10.11622/smedj.2016062 Concordance between core needle biopsy and surgical specimen for oestrogen receptor, progesterone receptor and human epidermal growth factor
More informationImmunohistochemical classification of breast tumours
Immunohistochemical classification of breast tumours Workshop in Diagnostic Immunohistochemistry September 19 th - 21 th 2018 Anne-Vibeke Lænkholm Department of Surgical Pathology, Zealand University Hospital,
More informationVENTANA ALK (D5F3) Rabbit Monoclonal Primary Antibody. ALK IHC Biomarker Testing Aiding in patient diagnosis
VENTANA (D5F3) Rabbit Monoclonal Primary Antibody IHC Biomarker Testing Aiding in patient diagnosis 2 IHC Biomarker Testing Lung cancer is the leading cause of death Lung cancer is the most prevalent form
More informationAdvantages and Disadvantages of Technologies for HER2 Testing in Breast Cancer Specimens
and of Technologies for HER2 Testing in Breast Cancer Specimens Daniela Furrer, MSc, 1-3 François Sanschagrin, PhD, 4,5 Simon Jacob, MD, 4,5 and Caroline Diorio, PhD 1-4 From the 1 Centre de recherche
More informationComparative Analysis of Methods Used in Breast Cancer HER2 and Sentinel Lymph Node Diagnosis
SHORT THESIS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY (Ph.D.) Comparative Analysis of Methods Used in Breast Cancer HER2 and Sentinel Lymph Node Diagnosis by Monika Francz MD Supervisor: Zoltán Szöllősi
More information2018 OPTIONS FOR INDIVIDUAL MEASURES: REGISTRY ONLY. MEASURE TYPE: Process
Quality ID #450 (NQF 1858): Trastuzumab Received By Patients With AJCC Stage I (T1c) III And HER2 Positive Breast Cancer Receiving Adjuvant Chemotherapy National Quality Strategy Domain: Effective Clinical
More informationKEY WORDS: Breast carcinoma, c-erbb2, Fluorescent. Mod Pathol 2001;14(11):
HER-2/neu in Breast Cancer: Interobserver Variability and Performance of Immunohistochemistry with 4 Antibodies Compared with Fluorescent In Situ Hybridization Thomas A. Thomson, M.D., Malcolm M. Hayes,
More informationInstant Quality FISH. The name says it all.
PRODUCT INFORMATION HER2 IQFISH pharmdx Instant Quality FISH Instant Quality FISH. The name says it all. HER2 IQFISH pharmdx IQ: Instant Quality every time. HER2 IQFISH pharmdx stains of a HER2 non-amplified
More informationInstant Quality FISH. The name says it all.
COMPANION DIAGNOSTICS Instant Quality FISH Instant Quality FISH. The name says it all. IQ: Instant Quality every time. Breast carcinoma stained with : Triple filter showing Blue DAPI colors nuclei, FITC
More informationBreast cancer diagnostic solutions Deliver diagnostic confidence
Breast cancer diagnostic solutions Deliver diagnostic confidence 2 Breast cancer diagnostic solutions Roche Tissue Diagnostics is committed to improving outcomes in breast cancer Breast cancer...the most
More informationProduct Introduction. Product Codes: HCL029, HCL030 and HCL031. Issue
Product Introduction Product Codes: HCL029, HCL030 and HCL031 Issue 1. 180510 Contents Introduction to Estrogen Receptor 2 ER immunohistochemistry 3 Quality control 5 Cell lines as controls 6 Estrogen
More informationDetection of Anaplastic Lymphoma Kinase (ALK) gene in Non-Small Cell lung Cancer (NSCLC) By CISH Technique
Cancer and Clinical Oncology; Vol. 7, No. 1; 2018 ISSN 1927-4858 E-ISSN 1927-4866 Published by Canadian Center of Science and Education Detection of Anaplastic Lymphoma Kinase (ALK) gene in Non-Small Cell
More informationIntroduction. The HER2 Testing Expert Panel has identified five Clinical Questions that form the core of this Focused Update.
Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/ College of American Pathologists Clinical Practice Guideline Focused Update Wolff, et al. Introduction
More informationSupplementary Online Content
Supplementary Online Content Fumagalli D, Venet D, Ignatiadis M, et al. RNA Sequencing to predict response to neoadjuvant anti-her2 therapy: a secondary analysis of the NeoALTTO randomized clinical trial.
More informationTrainableImmunohistochemicalHER2/neu Image Analysis. A Multisite Performance Study Using 260 Breast Tissue Specimens
TrainableImmunohistochemicalHER2/neu Image Analysis A Multisite Performance Study Using 260 Breast Tissue Specimens Aziza Nassar, MD, MPH; Cynthia Cohen, MD; Sally S. Agersborg, MD, PhD; Weidong Zhou,
More informationHormone receptor and Her2 neu (Her2) analysis
ORIGINAL ARTICLE Impact of Triple Negative Phenotype on Breast Cancer Prognosis Henry G. Kaplan, MD* and Judith A. Malmgren, PhD à *Swedish Cancer Institute at Swedish Medical Center; HealthStat Consulting
More information7/6/2015. Cancer Related Deaths: United States. Management of NSCLC TODAY. Emerging mutations as predictive biomarkers in lung cancer: Overview
Emerging mutations as predictive biomarkers in lung cancer: Overview Kirtee Raparia, MD Assistant Professor of Pathology Cancer Related Deaths: United States Men Lung and bronchus 28% Prostate 10% Colon
More informationMolecular Methods in the Diagnosis and Prognostication of Melanoma: Pros & Cons
Molecular Methods in the Diagnosis and Prognostication of Melanoma: Pros & Cons Ben J. Friedman, MD Senior Staff Physician Department of Dermatology Department of Pathology and Laboratory Medicine Henry
More informationBrief Formalin Fixation and Rapid Tissue Processing Do Not Affect the Sensitivity of ER Immunohistochemistry of Breast Core Biopsies
Brief Formalin Fixation and Rapid Tissue Processing Do Not Affect the Sensitivity of ER Immunohistochemistry of Breast Core Biopsies Victoria Sujoy, MD, Mehrdad Nadji, MD, and Azorides R. Morales, MD From
More information