Optimal use of a panel of methylation markers with GSTP1 hypermethylation in the diagnosis of prostate adenocarcinoma

Clin Cancer Res. 2004 Aug 15;10(16):5518-22. doi: 10.1158/1078-0432.CCR-04-0108.

Abstract

Purpose: In this study, we tested the ability of a panel of hypermethylation markers to improve the sensitivity of histologic prostate cancer detection in sextant needle biopsies.

Experimental design: We obtained fresh-frozen sextant biopsies from 72 excised prostates and directly compared blinded histologic review and quantitative real-time methylation-specific PCR for hypermethylation of four genes, Tazarotene-induced gene 1 (TIG1), adenomatous polyposis coli (APC), retinoic acid receptor beta2 (RARbeta2), and glutathione S-transferase pi (GSTP1) to detect the presence of prostate cancer. Results were compared with the final surgical pathological review of the resected prostates as the gold standard.

Results: Histologic review alone detected carcinoma with a sensitivity of 64% (39 of 61 cases) and 100% specificity. Quantitative real-time methylation-specific PCR for TIG1, APC, RARbeta2, and GSTP1 detected carcinoma with a sensitivity of 70%, 79%, 89%, and 75%, respectively, with 100% specificity for all of the genes. Using this panel of methylation markers in combination with histology resulted in the detection of 59 of 61 (97%) cases of prostate with 100% specificity, a 33% improvement over histology alone.

Conclusion: The use of a panel of methylation markers as an adjunct to histologic review may substantially augment prostate cancer diagnosis from needle biopsies.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acyltransferases / genetics*
  • Adenocarcinoma / genetics
  • DNA Methylation*
  • Genes, APC
  • Humans
  • Male
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / genetics*
  • Receptors, Retinoic Acid / genetics

Substances

  • Receptors, Retinoic Acid
  • retinoic acid receptor beta
  • Acyltransferases
  • fatty acyl ethyl ester synthase