Department of Pathology, Portuguese Oncology Institute of Lisboa, 1099-023 Lisboa, Portugal.
Cancer Biology & Epigenetics Group-Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), 4200-072 Porto, Portugal.
Int J Mol Sci. 2020 Apr 14;21(8):2715. doi: 10.3390/ijms21082715.
Male breast cancer (BC) is a distinct neoplasm with low but rising incidence, frequently diagnosed as advanced stage disease. Considering the relevance of altered homologous recombination repair (HRR) in male BC, we aimed to explore the biomarker potential of aberrant promoter methylation of , , , and .
Formalin-fixed paraffin-embedded (FFPE) tissue samples from 128 male BC patients, paired adjacent normal tissue and 19 gynecomastia cases were collected and assessed by quantitative methylation-specific PCR (qMSP). Non-parametric tests were used to compare methylation levels between tumor and non-tumor samples and to seek for associations with clinicopathological variables.
Only and disclosed significant differences between tumor and gynecomastia ( < 0.0001 and = 0.020, respectively). Assembled in a panel, and promoter methylation discriminated male BC from gynecomastia with 91.5% sensitivity, 89.5% specificity, and 91.2% accuracy. Moreover, promoter methylation levels were lower in paired non-tumor tissues, comparing to tumor samples. No associations were found between epigenetic alterations and clinicopathological features, as well as with RAD51 and XRCC3 immunoexpression and methylation levels.
Quantitative promoter methylation of and constitutes a promising and accurate biomarker for male BC. Validation in larger series and in liquid biopsies is warranted to confirm its usefulness in detection and monitoring settings.
男性乳腺癌（BC）是一种具有低但呈上升趋势发病率的独特肿瘤，常被诊断为晚期疾病。考虑到同源重组修复（HRR）改变在男性 BC 中的相关性，我们旨在探讨 、 、 、 和 异常启动子甲基化的生物标志物潜力。
收集了 128 例男性 BC 患者、配对的相邻正常组织和 19 例男性乳腺发育症病例的福尔马林固定石蜡包埋（FFPE）组织样本，并通过定量甲基化特异性 PCR（qMSP）进行评估。非参数检验用于比较肿瘤和非肿瘤样本之间的甲基化水平，并寻找与临床病理变量的关联。
仅 和 显示肿瘤与男性乳腺发育症之间存在显著差异（<0.0001 和 = 0.020）。将 和 组装成一个面板，可以以 91.5%的敏感性、89.5%的特异性和 91.2%的准确性区分男性 BC 与男性乳腺发育症。此外，与肿瘤样本相比，配对的非肿瘤组织中的启动子甲基化水平较低。未发现表观遗传改变与临床病理特征之间存在关联，也未发现与 RAD51 和 XRCC3 免疫表达和甲基化水平之间存在关联。
和 的定量启动子甲基化是男性 BC 有前途且准确的生物标志物。需要在更大的系列和液体活检中进行验证，以确认其在检测和监测中的有用性。
