J Urol. 2012 Sep 18. pii: S0022-5347(12)04906-3. doi: 10.1016/j.juro.2012.08.219. [Epub ahead of print]
Clinical Utility of an Epigenetic Assay to Detect Occult Prostate Cancer in Histopathologically Negative Biopsies: Results of the MATLOC Study.
Stewart GD, Van Neste L, Delvenne P, Delrée P, Delga A, McNeill SA, O'Donnell M, Clark J, Van Criekinge W, Bigley J, Harrison DJ.
Edinburgh Urological Cancer Group, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK.
Concern over possible false negative histopathology of prostate biopsies often leads to re-biopsy. A quantitative methylation-specific PCR (QMSP) assay panel, including GSTP1,APC and RASSF1, could serve to increase the sensitivity to detect cancer over pathologic review alone, leading towards a high negative predictive value (NPV) and a decrease of unnecessary repeat biopsies.
MATERIALS AND METHODS:
The MATLOC (Methylation Analysis To Locate Occult Cancer) study blindly tested archived prostate biopsy needle core tissue samples of 498 subjects from the UK and Belgium with histopathologically negative prostate biopsies followed by either a positive (cases) or negative (controls) repeat biopsy within 30 months. The clinical performance of the epigenetic marker panel, emphasizing NPV, was assessed and cross-validated. Multivariate logistic regression was used to evaluate all risk factors.
The epigenetic assay performed on the first, negative biopsies from this retrospective review cohort resulted in an NPV of 90% (95% CI, 87-93%). In a multivariate model, correcting for age, PSA, DRE and histopathological characteristics of the first biopsy, the epigenetic assay proved to be a significant, independent predictor of patient outcome with an odds ratio of 3.17 (95% CI, 1.81-5.53).
A multiplex QMSP assay determining the methylation status of GSTP1,APC and RASSF1is strongly associated with the outcome of a repeat biopsy up to 30 months after an initial negative biopsy in men with suspicion of prostate cancer. The addition of this epigenetic assay could improve the prostate cancer diagnostic process and reduce unnecessary repeat biopsies.
Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
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