Gene-specific hypermethylation (GSTP1) and global hypomethylation (LINE-1) on initial negative prostate biopsy as markers of prostate cancer on a rebiopsy.

Men at risk of missed prostate cancer (PCa) on a negative biopsy often undergo a rebiopsy. We evaluated if global hypomethylation, measured through LINE-1 methylation, and GSTP1 hypermethylation on a negative biopsy are associated with subsequent PCa diagnosis.

We performed a case-control study nested in an unselected series of 737 men who received at least two prostate biopsies at least three months apart at the Molinette Hospital, Turin, Italy. Two Pathology Wards were included for replication purposes. The study included 67 cases and 62 controls in Ward 1 and 62 cases and 66 controls in Ward 2. We used pyrosequencing to analyse LINE-1 and GSTP1 methylation in the negative biopsies. Odds ratios (OR) of PCa diagnosis were estimated using conditional logistic regression.

After mutual adjustment, GSTP1 hypermethylation was associated with an OR of PCa diagnosis of 5. 1 (95% confidence interval: 1. 7-14. 9) in Ward1 and 2. 0 (0. 8-5. 3) in Ward 2, while an association was suggested only for low LINE-1 methylation levels (<70 vs. 70-74%) with an OR of 2. 1 (0. 5-9. 1) in Ward1 and 1. 6 (0. 4-6. 1) in Ward 2. When the two Wards were combined the association was stronger for tumors with Gleason score ≥4+3 (GSTP1 hypermethylation: 9. 2 (2. 0-43. 1); LINE-1 (<70 vs. 70-74%): 9. 2 (1. 4-59. 3)). GSTP-1 alone improved the predictive capability of the model (p=0. 007).

GSTP1 hypermethylation on a negative biopsy is associated with the risk of PCa on a rebiopsy, especially of high grade PCa. Consistent results were found only for extremely low LINE-1 methylation levels.

Clinical cancer research : an official journal of the American Association for Cancer Research. 2015 Oct 16 [Epub ahead of print]

Renata Zelic, Valentina Fiano, Daniela Zugna, Chiara Grasso, Luisa Delsedime, Lorenzo Daniele, Diego Galliano, Andreas Pettersson, Anna Gillio-Tos, Franco Merletti, Lorenzo Richiardi

Department of Medical Sciences, University of Turin renatazelic@yahoo. com. , Cancer Epidemiology Unit, Cancer Epidemiology Unit, CeRMS and CPO-Piemonte, University of Turin. , Cancer Epidemiology Unit, CeRMS and CPO-Piemonte, University of Turin. , Cancer Epidemiology Unit, CeRMS and CPO-Piemonte, University of Turin. , Division of pathology, A. O. Città della Salute e della Scienza Hospital. , Division of pathology, A. O. Città della Salute e della Scienza Hospital. , Division of pathology, A. O. Città della Salute e della Scienza Hospital. , Department of medicine, Karolinska Institutet. , Cancer Epidemiology Unit, CERMS, University of Turin. , Unit of cancer Epidemiology, Unit of Cancer Epidemiology, University of Turin. , Department of medical Sciences, Cancer Epidemiology Unit, CeRMS and CPO-Piemonte, University of Turin.

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