Evaluation of GSTP1 and APC methylation as indicators for repeat biopsy in a high-risk cohort of men with negative initial prostate biopsies

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

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE: • To evaluate the performance of DNA methylation biomarkers in the setting of repeat biopsy in men with an initially negative prostate biopsy but a high index of suspicion for missed prostate cancer. PATIENTS AND METHODS: • We prospectively evaluated 86 men with an initial histologically negative prostate biopsy and high-risk features. • All men underwent repeat 12-core ultrasonography-guided biopsy. • DNA methylation of glutathione-S-transferase P1 (GSTP1) and adenomatous polyposis coli (APC) was determined using tissue from the initially negative biopsy and compared with histology of the repeat biopsy. • The primary outcome was the relative negative predictive value (NPV) of APC compared with GSTP1, and its 95% confidence interval (CI). RESULTS: • On repeat biopsy, 21/86 (24%) men had prostate cancer. • APC and GSTP1 methylation ratios below the threshold (predicting no cancer) produced a NPV of 0.96 and 0.80, respectively. The relative NPV was 1.2 (95% CI: 1.06-1.36), indicating APC has significantly higher NPV. • Methylation ratios above the threshold yielded a sensitivity of 0.95 for APC and 0.43 for GSTP1. • Combining both methylation markers produced a performance similar to that of APC alone. • APC methylation patterns were consistent with a possible field effect or occurrence early in carcinogenesis. CONCLUSIONS: • APC methylation provided a very high NPV with a low percentage of falsenegatives, in the first prospective study to evaluate performance of DNA methylation markers in a clinical cohort of men undergoing repeat biopsy. • The potential of APC methylation to reduce unnecessary repeat biopsies warrants validation in a larger prospective cohort.

Original languageEnglish (US)
Pages (from-to)56-62
Number of pages7
JournalBJU International
Volume110
Issue number1
DOIs
StatePublished - Jul 2012

Keywords

  • APC
  • Biopsy
  • GSTP1
  • Methylation
  • Prostate cancer

ASJC Scopus subject areas

  • Urology

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