Quantitative GSTP1 methylation clearly distinguishes benign prostatic tissue and limited prostate adenocarcinoma.
OBJECTIVE
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.


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.
Harden
Susan V
SV
Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Division, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Guo
Zhongmin
Z
Epstein
Jonathan I
JI
Sidransky
David
D
D000230:Adenocarcinoma / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis*; D019175:DNA Methylation; D003937:Diagnosis, Differential; D015870:Gene Expression; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000032:analysis* / Q000235:genetics; D008297:Male; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000737:chemistry; D011469:Prostatic Diseases / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D007527:Isoenzymes; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase