Azad Mohammed Kamal Elden. Evaluation of Acid and Alkaline Phosphates in Benign Prostatic Hyperplasia and. Patients.

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1 Evaluation of Acid and Alkaline Phosphates in Benign Prostatic Hyperplasia and Prostatic Cancer Azad Mohammed Kamal Elden Abstract Tumors of prostate are common diseases that afflict the aging male population and second leading of death by prostate cancer Prostatic tumor can be classified into two types' benign prostatic hyperplasia (BPH), and prostatic cancer (PCa). The aim of this study is to verify the levels of alkaline phosphatase(alp), acid phosphatase(acp) and prostatic acid phospatase (PAP) in BPH and PCa patients. This study was carried out during the period from January to December One hundred two patients complaining from prostatic tumors and disorder in urination, their ages matches (54-85) year admitted to Al-Rezgari general hospital in Erbil. Clinical investigation for all patients done by specialist doctors for differentiate between BPH and PCa patients. Five milliliter of blood was drawn from each patients in addition to twenty healthy male as control group measurement of ALP, ACP and PAP enzymes. Among 102 patients the number and percentage of BPH patients were 74 (73%), while the number and percentage of PCa patients were 28(27%). It was observed that 22(79%) of PCa patients have localized PCa, while 6(21%) of them have metastatic PCa and the mean levels of ALP. ACP and PAP were highly significantly increased in metastatic PCa, while, in localized PCa patients only the mean levels of ACP and PAP were highly significantly increased. In BPH patients only the mean level of PAP was highly significantly increased. This study showed that the mean levels of ALP, ACP and the PAP were highly significantly increased in metastatic PCa patients, while in localized PCa only the mean levels of ACP and PAP were highly significantly increased. In BPH patients only the mean level of PA was highly significantly increased. Introduction Prostatic tumors regarded as male population diseases male commonly after 50 years of age may afflicted by prostatic tumors. This tumor may be BPH or PCa, this influence by many factors like age, diet alcohol, smoking, sexually behavior and hormonal status (1). In aging male the prostatic gland may enlarged due to action of testosterone hormone because testosterone hormone regarded as anabolic hormone, male after puberty and prolong exposuring of prostatic gland to testosterone hormone may led to increased the numbers of prostatic cells and decreased cells death rate an imbalance occurs between cells death and cells divisions in prostatic gland may lead to enlargement in prostatic gland and compresses on urethra and dysfunction occurs in urination. Mutation in androgen receptors and in P53 gene expression which controlling of cells division may enhancement in prostatic tumors (2) Prostatic cancer is the second most common malignancy found in men and is 88 Tikrit Medical Journal 2010; 16(2):88 93 responsible for the highest rate of morbidity after lung cancer. Infection and mutation in androgen receptors and testosterone hormone play roles in metastasis prostatic tumors (3). Acid phosphatases are enzymes that are widely distributed in tissues, including bone, liver, spleen, kidney red blood cells, platelets, However greatest diagnostic importance involves the prostate gland were ACP activity is 100 times higher in other tissues. Immunochemical methods are highly specific for determining the prostatic fraction (4). Human prostatic acid phosphatase (hpap) is a glycoprotein synthesized in the epithelial cells of the prostate gland (5) from which it is secreted into prostatic fluid (6). This enzyme hydrolyzes a wide range of alkyl and aryl orthophosphate monoesters, including phosphotyrosine (6) and has also been found to dephosphorylate macromolecules, such as phosphopeptides and phosphoproteins hpap is

2 categorized as an acid phosphatase, since in has an optimum ph of 4-6 (7). Human prostatic acid phosphatase (PAcP) is a prostate epithelium-specific differentiation antigen. Cellular PAcP functions as a neutral protein tyrosine phosphatase and is involved in regulating androgen-promoted prostate cancer cell proliferation. There are two forms of PAcP: the cellular and the secretory forms. The intracellular level of PAcP is decreased, correlating with prostate carcinogenesis but its increased in circulation may serve as a marker for cancer diagnosis (8). The cellular form of PAcP functions as a neutral protein tyrosine phosphatase and is involved in regulating cell growth by dephosphorylating ErbB-2 gene in human prostate cancer cells. Cellular PAcP is also involved in regulating non-genomic, androgenpromoted prostate cell proliferation. The regulation of PAcP expression and secretion has been of long-standing interest. In the past five decades., PAcP secretion has served as a marker for androgen action (9).Nuclear run-on experiments have revealed that androgens can regulate PAcP expression at the transcriptional level is found in cells of the prostate, liver, erythrocytes, platelets and bone and is regarded as tumor marker for prostatic cancer and main indication for estimation are to help diagnose prostatic carcinoma and monitor its treatment (10). Alkaline phosphatases (ALP) are group of enzyme which hydrolyzes phosphatase at high PH. ALP regarded as tumor marker for bone cancer metastasis (10). They are present in most tissues but are particularly highly concentrated in the osteoblasts of bone that participate in calcification of bone, even that found in hepatobiliary tract, intestinal wall, renal tubules and placenta (11). Elevation of ALP concentration in prostate cancer means metastatic of prostate cancer, and is major cause of death in patients with advanced prostate cancer, the most frequent site for metastatic lesions being the bone. Increasing in ALP concentration explain if cancer is metastasis to bone (coccyx) causing sarcoma (12). Material and methods This study was carried out during the period from January to December 2009.One hundred two patients' 102 patients with prostatic tumor were admitted to urology department in Al-Rezgari general hospital their ages matches (54-85) year. Clinical investigation, and histopathological examination done for each patient by specialist doctor for differentiated between BPH and PCa patients Five milliliter (5ml) of blood was drawn from each patient in addition to twenty healthy male regarded as control group for measurement of ALP, ACP and PAP enzymes. Enzymes levels were measured by using colorimetric spectrophotometer Cessel at 405 nanometer (nm). Enzymatic BIMERIUX kit used for measurement of ALP and RANDOX kit for measurement of ACP and PAP concentration Results Among 102 patients the results revealed that the number and percentage of BPH patients were 28(27%), while the number and percentage of PCa were 74 (73%) as illustrated in figure (1). The results revealed that the number and percentage of localized PCa patients were 6 (21%), while the number and percentage of metastatic PCa patients were 22(79%) as shown in Figure (2). The data observed a highly significant increase in the mean levels of ALP, ACP and PAP in metastatic PCa patients (180± 19.2, 57.06±5.2 and 51.06±8.3) U/L respectively, in comparison to control group (64.8±10.9, 6.1±0.9and 2.46±0.4)U/L respectively (P<0.001), as illustrated in figure (3). According to localized PCa the data revealed that the mean levels of ACP and PAP were significantly higher increase (11.8±0.89 and 8.9±0.7) U/L respectively in comparison to control group (6.1±0.9 and 2.46±0.4)U/L (P<0.001) respectively, while no significant increase was observed in the mean level of ALP (66.04±7.2) U/L in comparison to control group(64.8±10.9) U/L (P>0.05) as shown in figure(4). In BPH patients the mean Tikrit Medical Journal 2010; 16(2):

3 level of PAP highly significantly increase(5 ±0.8) U/L, in comparison to control group ((2.46±0.4)U/L (P<0.001), while no significant difference observed in the mean level of ALP and ACP (66.9± 16.6 and 6.4±1.6) U/L respectively in comparison to control group( 64.8±10.9 and 6.1±0.9) respectively U/L(P>0.05)as illustrated in,,figure(5) Discussion The results observed that the mean levels of ALP, ACP and PAP were highly significantly increased in metastatic PCa patients in comparison to control group as illustrated in figure(3), while in localized PCa patients only the mean levels of ACP and PAP were highly significantly increased in comparison to control group as shown in figure (4). In BPH patients the data revealed that only the mean level of PAP was highly significant increased in comparison to control group as illustrated in figure (5). In metastatic PCa patients the increasing in ALP concentration was may be due to increase in ALP enzymes activities in bone because it s the main source of ALP enzymes, and responsible for calcification of bone and metastatic of cancer to bone may lead to fractionation of bone and causing increase the infiltration of enzyme to circulation therefore the mean level of ALP is significantly increase in metastatic than localized PCa and BPH patients, and this is in agreement with that found by Junk K et al et al they found that increasing of serum ALP enzyme are found in patients with advanced PCa with bone metastatic compared to patients with local disease and patients with benign prostatic hyperplasia(9) The results revealed that acid phosphatases levels was highly significantly increased in metastatic PCa patients in comparison to control group since ACP are a group of five ubiquitous tissue isoenzymes that hydrolyze organic monophosphate esters when patient afflicted by PCa and dephophorylate of Nuclear Factor KB(NK-kb) in order to increase gene expression for cytokine as defense mechanism against tumor cells even that increased of fractionation of prostatic cells due to prostatic cancer cell may lead to increase PAP infiltration in circulation. PAP is a potential tumor-associated antigen in prostate cancer, given that expression of PAP is essentially restricted to prostate tissue including metastatic prostate cancer this may lead to increase the level in PCa patients(10). In BPH patients the PAP level was highly significantly increased this may be due to increase in the number of cell due to an imbalance occurred between cell division and cell death, and this require to protein synthesis through phosphrylation and deceased of P53 gene expression in old male patients may led to uncontrolled cell division this in agreement with that found by Lin,M,F et al they found that PAP level increase, and is a potential tumor-associated antigen in PCa and BPH a given that expression of PAP is essentially restricted to prostate tissue including metastatic prostate cancer and benign prostatic tumor (11). CONCLUSION 1. Alkaline phosphatase (ALP), acid phosphatase (ACP) and prostatic acid phosphatase (PAP) levels were highly significantly increased in metastasis prostatic cancer patients. 2. Acid phosphatase (ACP) and prostatic acid phosphatase(pap) levels were highly significant increased in localized prostatic cancer 3. Prostatic acid phosphatase (PAP) level was only significantly. increased in benign prostatic hyperplesia (BPH). Recommendation According to these results we recommended for measurement of ALP, ACP and PAP enzymes concentration together with other clinical investigation in patients suspected with prostatic disorders in order to help the doctor and give him a picture on patients status for proper treatment 90 Tikrit Medical Journal 2010; 16(2):88 93

4 28 (27%) BPH PCA 74 (73%) Figure: (1) Number and percentage of BPH and PCa patients 6( 21%) 22 (79%) Metastatic PCA localized PCA Figure (2): Number and percentage of localized and metastasis PCa patients Tikrit Medical Journal 2010; 16(2):

5 Mean level U/L ALP ACP PAP Metastasis Pca Control Figure( 3 ) Mean levels of ALP, ACP and PAP U/L in metastasis PCa patients Mean levelu/l Localized Pca Control 0 ALP ACP PAP Figure( 4 ) Mean level of ALP, ACP and PAP U/L in localized PCa patients 92 Tikrit Medical Journal 2010; 16(2):88 93

6 Mean levelu/l BPH Patients Control 0 ALP ACP PAP Figure( 5 ) Mean level of ALP, ACP and PAP U/L in BPH patients Tikrit Medical Journal 2010; 16(2):