Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University, Ministry of Education, Tianjin, China.
Department of Pathology, Tianjin Union Medical Center, Tianjin People's Hospital, Tianjin, China.
Histopathology. 2018 Nov;73(5):819-831. doi: 10.1111/his.13699. Epub 2018 Aug 23.
The mechanism of androgen receptor (AR) promoting tumour growth in oestrogen receptor-negative (ER ) breast cancer (BC) is undetermined. Prostate-derived ETS factor (PDEF) is highly restricted to the hormone-regulated tissues of epithelial cells, such as those in the prostate, breast and other tissues. It has been demonstrated that PDEF expression is associated with AR in prostate cancer. In this research, we aimed to investigate the relationship between PDEF and AR in ER BC.
We immunohistochemically evaluated the correlation between PDEF and AR expression in 246 cases of ER invasive BC, and investigated their relationship in ER BC cell lines. The expression of PDEF was associated with the positive expression of AR (P < 0.001) and a worse survival rate (P = 0.006). PDEF tumours were significantly more often AR (P < 0.001). AR and PDEF were more often co-expressed and the series of AR PDEF (126 of 246, 51.2%) had a poor survival rate (P = 0.046). In Cox models, PDEF expression (P = 0.028) was an independent predictor for overall survival (OS). At the cellular protein and mRNA levels, our experiments also showed a statistically significant positive correlation between PDEF and AR, and that PDEF may be regulated by AR.
PDEF is associated with markers of bad prognosis, supporting its role as a growth promoter in ER BC. Our findings also provide evidence that PDEF is strongly correlated with AR expression in ER breast cancer; it may be a downstream target gene of AR and a potential prognostic factor in ER BC.
雄激素受体(AR)促进雌激素受体阴性(ER)乳腺癌(BC)肿瘤生长的机制尚不清楚。前列腺衍生的 ETS 因子(PDEF)高度局限于激素调节的上皮细胞组织,如前列腺、乳腺和其他组织。已经证明,PDEF 表达与前列腺癌中的 AR 相关。在这项研究中,我们旨在研究 PDEF 和 ER BC 中 AR 之间的关系。
我们通过免疫组织化学方法评估了 246 例 ER 浸润性 BC 中 PDEF 和 AR 表达的相关性,并在 ER BC 细胞系中研究了它们之间的关系。PDEF 的表达与 AR 的阳性表达相关(P<0.001),且生存预后较差(P=0.006)。PDEF 肿瘤中 AR 的表达明显更高(P<0.001)。AR 和 PDEF 常同时表达,且 AR-PDEF 系列(246 例中有 126 例,占 51.2%)生存预后较差(P=0.046)。在 Cox 模型中,PDEF 表达(P=0.028)是总生存(OS)的独立预测因子。在细胞蛋白和 mRNA 水平上,我们的实验还表明 PDEF 和 AR 之间存在统计学上显著的正相关,并且 PDEF 可能受 AR 调节。
PDEF 与不良预后标志物相关,支持其在 ER BC 中作为生长促进剂的作用。我们的研究结果还提供了证据,表明 PDEF 在 ER 乳腺癌中与 AR 表达密切相关;它可能是 AR 的下游靶基因,也是 ER BC 的潜在预后因素。