PROSTATE CANCER IN SOUTHWEST PAKISTAN: MOLECULAR DETECTION BY METHYLATION-SPECIFIC PCR FROM URINE SPECIMENS

Main Article Content

Muhammad Hashim Mengal
Muhammad Kamran Taj
Imran Nawaz

Keywords

Prostate cancer, Benign prostatic hyperplasia, Methylation-specific polymerase chain reaction, Glutathione S-transferase P1

Abstract

Introduction: Prostate cancer (PCa) represents the second most prevalent malignancy among males, which is characterized by a high mortality rate. The aim of our study was to evaluate the methylation status of glutathione S-transferase P1 (GSTP1) in urine specimens from males with PCa and benign prostatic hyperplasia (BPH) and its usefulness in distinguishing between males with PCa and BPH by non-invasive methods.


Methodology: Voided urine specimens were collected from 78 patients with PCa and 57 patients with BPH. Genomic DNA was isolated and subjected to bisulfite modification. Methylation status of the GSTP1 gene was determined by conventional methylation-specific polymerase chain reaction (MSP) analysis.


Results: Promoter hyper methylation of the GSTP1 gene in voided urine samples was found in 71 of 78 (91%) males with PCa and in 7 of 57 (12%) males with BPH. The sensitivity and specificity of GSTP1 in discriminating between PCa and BPH males were 97% and 88%, respectively.


Conclusion: Gene analysis of GSTP1 using conventional MSP in urine specimens can be used as a non-invasive biomarker to distinguish between men with malignant and benign prostatic diseases.


 

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References

1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010; 60: 277–300.
2. Garcia M, Jemal A, Ward EM, Center MM, Hao Y, Siegel RL, et al. Global Cancer Facts & Figures 2007. Atlanta, (GA): American Cancer Society; 2007: 1–50.
3. Greene KL, Albertsen PC, Babaian RJ, Carter HB, Gann PH, Han M, et al. Prostate specific antigen best practice statement: 2009 update. J Urol 2009; 182: 2232–41.
4. Nakayama M, Gonzalgo ML, Yegnasubramanian S, Lin X, De Marzo AM, Nelson WG. GSTP1 CpG island hypermethylation as a molecular biomarker for prostate cancer. J Cell Biochem 2004; 91: 540–52.
5. Ellinger J, Muller SC, Stadler TC, Jung A, Von Ruecker A, Bastian PJ. The role of cell-free circulating DNA in the diagnosis and prognosis of prostate cancer. Urol Oncol 2011; 29 (2): 124–9.
6. Nakayama M, Bennett CJ, Hicks JL, Epstein JI, Platz EA, Nelson WG, et al. Hyper methylation of the human glutathione S-transferase P1 gene (GSTP1) CpG is present in a subset of proliferative inflammatory atrophy lesions but not in normal or hyperplastic epithelium of the pro state: a detailed study using laser-capture microdissection. Am J Pathol 2003; 163: 923.
7. Jeronimo C, Usadel H, Henrique R, Silva C, Oliveira J, Lopes C, et al. Quantitative GSTP1 hyper methylation in bodily fluids of patients with prostate cancer. Urology 2002; 60: 1131–5.
8. Cairns P, Esteller M, Herman JG, Schoenberg M, Jero nimo C, Sanchez-Cespedes M, et al.Molecular detection of prostate cancer in urine by GSTP1 hyper methylation. Clin Cancer Res 2001; 7: 2727–30.
9. American Joint Committee on Cancer. Genitourinary sites. In: Edge S.B, Byrd D.R, Compton C.C, Fritz A.G, Greene F.L, Trotti A (Eds). AJCC cancer staging manual. 7th ed. New York: Springer; 2010: 457–69.
10. Billis A, Grimaraes MS, Freitas LL, Meirells L, Magna LA, dard Gleason grading of prostatic carcinoma in needle biopsies. J Urol 2008; 180(2): 548–52.
11. Hopkins TG, Burns PA, Routledge MN. DNA methylation of GSTP1 as a biomarker in diagnosis of prostate cancer. Urology 2007; 69: 11–16.
12. Zou KH, O’Mulley AJ, Mauri L. Receiver-operating characteristic analysis for evaluating diagnostic tests and predictive models. Circulation, 2007; 115: 654–7.
13. Payne SR, Serth J, Schostak M, Kamradt J, Strauss A, Thelen P, et al. DNA methylation biomarkers of prostate cancer: confirmation of candidates and evidence urine is the most sensitive body fluid for non-invasive detection. Prostate 2009; 69: 1257–69.
14. Gonzalgo ML, Nakayama M, Lee SM, De Marzo AM, Nelson WG. Detection of GSTP1 methylation in prostatic secretions using combinatorial MSP analysis. Urology 2004; 63: 414–8.
15. Ahmed H. Promoter methylation in prostate cancer and its application for the early detection of prostate cancer using serum and urine samples. Biomark Cancer 2010; 2010: 17–33.
16. De Marzo AM, Platz EA, Sutcliffe S, Xu J, Gronberg H, Nelson WG, et al. Inflammation in prostate carcinogenesis. Nat Rev Cancer 2007; 7(4): 256–69.
17. Goessl C, Muller M, Heicappell R, et al. DNA-based de tection of prostate cancer in urine after prostatic massage. Urology 2001; 58: 335–8.
18. Woodson K, O’Relly KJ, Hanson JC, Nelson D, Walk EL, Tangrea JA. The usefulness of the detection of GSTP1 methylation in urine as a biomarker in the diagnosis of prostate cancer. The Journal of Urology, 2008; 179(2): 508–12.
19. Alumkal JJ, Zhang Z, Humphreys EB, Bennett C, Man gold LA, Carducci MA, et al. Effect of DNA methylation on identification of aggressive prostate cancer. Urology 2008; 72: 1234–9.

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