Quantitative Gstp1 Methylation Clearly Distinguishes Benign Prostatic Tissue And Limited Prostate Adenocarcinoma (2003)

No AccessJournal of UrologyINVESTIGATIVE UROLOGY1 Mar 2003Quantitative Gstp1 Methylation Clearly Distinguishes Benign Prostatic Tissue And Limited Prostate Adenocarcinoma SUSAN V. HARDEN, ZHONGMIN GUO, JONATHAN I. EPSTEIN, and DAVID SIDRANSKY SUSAN V. HARDENSUSAN V. HARDEN , ZHONGMIN GUOZHONGMIN GUO , JONATHAN I. EPSTEINJONATHAN I. EPSTEIN , and DAVID SIDRANSKYDAVID SIDRANSKY View All Author Informationhttps://doi.org/10.1097/01.ju.0000049627.90307.4dAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Hypermethylation of the glutathione S-transferase gene (GSTP1) is the most common (greater than 90%) reported epigenetic alteration in prostate cancer. It occurs early in cancer progression and it is a promising marker for detecting organ confined disease. To evaluate its use as a diagnostic tool for cancer we used quantitative GSTP1 methylation to test for the presence of cancer in 45 prostate needle biopsy samples. Materials and Methods: Paraffin tissue samples from 45 patients with minute foci of intermediate grade prostatic adenocarcinoma or benign disease on needle biopsy were tested for GSTP1 hypermethylation using quantitative fluorogenic real-time methylation specific polymerase chain reaction. This assay was performed in blinded fashion without previous knowledge of the histopathological diagnosis. Results: DNA from 29 of the 45 paraffin samples was amenable to polymerase chain reaction amplification. In these 29 samples GSTP1 methylation was detected in 11 of 15 cases of limited cancer and in 0 of 14 of benign disease (2-sided Fisher's exact test, p <0.0001). Thus, this assay had 73% sensitivity, 100% specificity, 100% positive and 78% negative predictive values. Conclusions: Quantitation of GSTP1 hypermethylation accurately detects the presence of cancer even in small, limited tissue samples. It represents a promising diagnostic marker that could be used as an adjunct to tissue biopsy as part of prostate cancer screening. References 1 : Cancer statistics, 2001. CA Cancer J Clin2001; 51: 15. Crossref, Medline, Google Scholar 2 : Long-term biochemical disease-free and cancer-specific survival following anatomic radical retropubic prostatectomy. The 15-year Johns Hopkins experience. Urol Clin North Am2001; 28: 555. Google Scholar 3 : CG island methylation changes near the GSTP1 gene in prostatic carcinoma cells detected using the polymerase chain reaction: a new prostate cancer biomarker. Cancer Epidemiol Biomarkers Prev1997; 6: 443. Google Scholar 4 : Cytidine methylation of regulatory sequences near the pi-class glutathione S-transferase gene accompanies human prostatic carcinogenesis. Proc Natl Acad Sci USA1994; 91: 11733. Google Scholar 5 : CG island methylation changes near the GSTP1 gene in prostatic intraepithelial neoplasia. Cancer Epidemiol Biomarkers Prev1998; 7: 531. Google Scholar 6 : Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA1996; 93: 9821. Crossref, Medline, Google Scholar 7 : Inactivation of glutathione S-transferase P1 gene by promoter hypermethylation in human neoplasia. Cancer Res1998; 58: 4515. Google Scholar 8 : Real time quantitative PCR. Genome Res1996; 6: 986. Google Scholar 9 : MethyLight: a high-throughput assay to measure DNA methylation. Nucleic Acids Res2000; 28: E32. Google Scholar 10 : Quantitation of GSTP1 methylation in non-neoplastic prostatic tissue and organ-confined prostate adenocarcinoma. J Natl Cancer Inst2001; 93: 1747. Google Scholar 11 : Molecular detection of tumor cells in bronchoalveolar lavage fluid from patients with early stage lung cancer. J Natl Cancer Inst1999; 91: 332. Google Scholar 12 : A modified and improved method for bisulphite based cytosine methylation analysis. Nucleic Acids Res1996; 24: 5064. Google Scholar 13 : Quantitative adenomatous polyposis coli promoter methylation analysis in tumor tissue, serum, and plasma DNA of patients with lung cancer. Cancer Res2002; 62: 371. Google Scholar 14 : CpG island hypermethylation in human colorectal tumors is not associated with DNA methyltransferase overexpression. Cancer Res1999; 59: 2302. Google Scholar 15 : Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science1988; 239: 487. Google Scholar 16 : Serial prostatic biopsies in men with persistently elevated serum prostate specific antigen values. J Urol1994; 151: 1571. Link, Google Scholar 17 : Evaluation of cytologic techniques for diagnosis of prostate cancer. Urology1983; 21: 417. Google Scholar From the Departments of Otolaryngology-Head and Neck Surgery (Head and Neck Cancer Research Division), Pathology, Urology and Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland© 2003 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byStewart G, Van Neste L, Delvenne P, Delrée P, Delga A, McNeill S, O'Donnell M, Clark J, Van Criekinge W, Bigley J and Harrison D (2013) Clinical Utility of an Epigenetic Assay to Detect Occult Prostate Cancer in Histopathologically Negative Biopsies: Results of the MATLOC StudyJournal of Urology, VOL. 189, NO. 3, (1110-1116), Online publication date: 1-Mar-2013.ZHOU M, TOKUMARU Y, SIDRANSKY D and EPSTEIN J (2018) QUANTITATIVE GSTP1 METHYLATION LEVELS CORRELATE WITH GLEASON GRADE AND TUMOR VOLUME IN PROSTATE NEEDLE BIOPSIESJournal of Urology, VOL. 171, NO. 6 Part 1, (2195-2198), Online publication date: 1-Jun-2004. Volume 169Issue 3March 2003Page: 1138-1142 Advertisement Copyright & Permissions© 2003 by American Urological Association, Inc.Keywordstumor markers, biologicalprostatic neoplasmsgene expressionprostateglutathione transferaseMetricsAuthor Information SUSAN V. HARDEN Equal study contribution. More articles by this author ZHONGMIN GUO Equal study contribution. More articles by this author JONATHAN I. EPSTEIN More articles by this author DAVID SIDRANSKY Financial interest and/or other relationship with Virco, Inc. More articles by this author Expand All Advertisement PDF downloadLoading ...