Choi Jung Eun, Kang Su Hwan, Lee Soo Jung, Bae Young Kyung
Department of Surgery, Yeungnam University College of Medicine, Daegu, South Korea.
Tumour Biol. 2014 Dec;35(12):12255-63. doi: 10.1007/s13277-014-2534-4. Epub 2014 Sep 2.
B cell lymphoma/leukemia-2 (Bcl-2) expression has generally been associated with estrogen receptor positivity and favorable prognosis in breast cancer. We examined immunohistochemical expression of Bcl-2 in 492 triple-negative breast cancers (TNBCs) using tissue microarrays and investigated its correlation with clinicopathologic features and clinical outcome. A total of 47 (9.5 %) TNBCs showed Bcl-2 expression. Bcl-2 expression was not associated with any of the clinicopathologic parameters and did not affect patient survival in TNBCs (Bcl-2-positive vs Bcl-2-negative TNBCs; overall survival (OS), P = 0.258; disease-free survival (DFS), P = 0.436). When TNBCs were divided into basal (cytokeratin 5/6 (CK5/6)+ and/or epidermal growth factor receptor (EGFR)+) and non-basal (CK5/6- and EGFR-) subgroups, Bcl-2 expression showed a significant association with worse OS (P = 0.002) and DFS (P = 0.002) in the non-basal subgroup. Among patients treated with an anthracycline, Bcl-2 expression also showed an association with decreased survival (OS, P = 0.004; DFS, P = 0.003) in the non-basal subgroup. In multivariate analyses, Bcl-2 expression was an independent poor prognostic factor for OS (P = 0.003) and DFS (P = 0.002) in this subgroup of TNBCs. Our results suggest that positive expression of Bcl-2 predicts no benefit from adjuvant anthracycline-based chemotherapy in non-basal TNBC patients. In conclusion, Bcl-2 status showed both prognostic and predictive values in non-basal TNBCs; therefore, assessment of Bcl-2 status and basal phenotype can provide information on prognostic and therapeutic classifications of TNBCs.
B细胞淋巴瘤/白血病-2（Bcl-2）的表达通常与乳腺癌中的雌激素受体阳性及良好预后相关。我们使用组织芯片检测了492例三阴性乳腺癌（TNBC）中Bcl-2的免疫组化表达，并研究了其与临床病理特征及临床结局的相关性。共有47例（9.5%）TNBC显示Bcl-2表达。Bcl-2表达与任何临床病理参数均无关联，且不影响TNBC患者的生存（Bcl-2阳性与Bcl-2阴性TNBC；总生存期（OS），P = 0.258；无病生存期（DFS），P = 0.436）。当将TNBC分为基底样（细胞角蛋白5/6（CK5/6）+和/或表皮生长因子受体（EGFR）+）和非基底样（CK5/6-和EGFR-）亚组时，Bcl-2表达在非基底样亚组中与较差的OS（P = 0.002）和DFS（P = 0.002）显著相关。在接受蒽环类药物治疗的患者中，Bcl-2表达在非基底样亚组中也与生存率降低相关（OS，P = 0.004；DFS，P = 0.003）。在多变量分析中，Bcl-2表达是该TNBC亚组中OS（P = 0.003）和DFS（P = 0.002）的独立不良预后因素。我们的结果表明，Bcl-2的阳性表达预示非基底样TNBC患者无法从基于蒽环类药物的辅助化疗中获益。总之，Bcl-2状态在非基底样TNBC中显示出预后和预测价值；因此，评估Bcl-2状态和基底样表型可为TNBC的预后和治疗分类提供信息。
