Cancer Epidemiology Unit-CERMS, Department of Medical Sciences, University of Turin, and CPO-Piemonte, Turin, Italy.
Division of Pathology, A.O. Città della Salute e della Scienza Hospital, Turin, Italy.
Clin Cancer Res. 2016 Feb 15;22(4):984-92. doi: 10.1158/1078-0432.CCR-15-0606. Epub 2015 Oct 16.
Men at risk of missed prostate cancer on a negative biopsy often undergo a rebiopsy. We evaluated whether global hypomethylation, measured through LINE-1 methylation, and GSTP1 hypermethylation on a negative biopsy are associated with subsequent prostate cancer 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 analyze LINE-1 and GSTP1 methylation in the negative biopsies. Odds ratios (OR) of prostate cancer diagnosis were estimated using conditional logistic regression.
After mutual adjustment, GSTP1 hypermethylation was associated with an OR of prostate cancer diagnosis of 5.1 (95% confidence interval: 1.7-14.9) in Ward 1 and 2.0 (0.8-5.3) in Ward 2, whereas 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 Ward 1 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 prostate cancer on a rebiopsy, especially of high-grade prostate cancer. Consistent results were found only for extremely low LINE-1 methylation levels.
在阴性前列腺活检中，有漏诊前列腺癌风险的男性通常会进行再次活检。我们评估了阴性活检中 LINE-1 甲基化和 GSTP1 高甲基化的整体低甲基化是否与随后的前列腺癌诊断有关。
我们进行了一项病例对照研究，该研究嵌套在意大利都灵 Molinette 医院进行的一项未选择的 737 名男性的系列研究中，这些男性至少进行了两次至少相隔三个月的前列腺活检。为了复制目的，包括了两个病理病房。该研究包括 1 号病房的 67 例病例和 62 例对照，2 号病房的 62 例病例和 66 例对照。我们使用焦磷酸测序分析阴性活检中的 LINE-1 和 GSTP1 甲基化。使用条件逻辑回归估计前列腺癌诊断的优势比（OR）。
相互调整后，GSTP1 高甲基化与 1 号病房（OR=5.1，95%置信区间：1.7-14.9）和 2 号病房（OR=2.0，0.8-5.3）的前列腺癌诊断的 OR 相关，而低 LINE-1 甲基化水平（<70%与 70%-74%）与 1 号病房（OR=2.1，0.5-9.1）和 2 号病房（OR=1.6，0.4-6.1）的 OR 相关。当两个病房合并时，Gleason 评分≥4+3 的肿瘤的相关性更强 [GSTP1 高甲基化：9.2（2.0-43.1）；LINE-1（<70%与 70%-74%）：9.2（1.4-59.3）]。单独使用 GSTP1 可提高模型的预测能力（P=0.007）。
阴性活检中的 GSTP1 高甲基化与再次活检中的前列腺癌风险相关，尤其是高级别前列腺癌。仅发现极低的 LINE-1 甲基化水平存在一致结果。
