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.
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.
Authors: Bruce J Trock; Michelle J Brotzman; Leslie A Mangold; Joseph W Bigley; Jonathan I Epstein; David McLeod; Eric A Klein; J Stephen Jones; Songbai Wang; Theresa McAskill; Jyoti Mehrotra; Bhargavi Raghavan; Alan W Partin Journal: BJU Int Date: 2011-11-11 Impact factor: 5.588
Authors: Saskia M Wilting; Wina Verlaat; Annelieke Jaspers; Nour A Makazaji; Reuven Agami; Chris J L M Meijer; Peter J F Snijders; Renske D M Steenbergen Journal: Epigenetics Date: 2013-01-16 Impact factor: 4.528
Authors: K A van Nifterik; J van den Berg; W F van der Meide; N Ameziane; L E Wedekind; R D M Steenbergen; S Leenstra; M V M Lafleur; B J Slotman; L J A Stalpers; P Sminia Journal: Br J Cancer Date: 2010-06-01 Impact factor: 7.640
Authors: Saskia M Wilting; Robert A A van Boerdonk; Florianne E Henken; Chris J L M Meijer; Begona Diosdado; Gerrit A Meijer; Carlos le Sage; Reuven Agami; Peter J F Snijders; Renske D M Steenbergen Journal: Mol Cancer Date: 2010-06-26 Impact factor: 27.401