Abd-Elazeem Mona A, Abd-Elazeem Marwa A
Pathology Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
Pathology Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
Ann Diagn Pathol. 2015 Feb;19(1):37-42. doi: 10.1016/j.anndiagpath.2014.10.003. Epub 2014 Oct 25.
Breast cancer is the most common malignancy in women and the leading cause of cancer mortality worldwide. Triple-negative breast cancer (TNBC) is an important phenotype of breast cancer that accounts for a relatively small number of breast cancer cases but still represent a focus of increasing interest at the clinical, biological, and epidemiological level. Claudins are the major component of the tight junction, and only a few studies have addressed the role of claudins in breast cancer, especially TNBC. Androgen receptors (ARs), as members of the nuclear receptor superfamily, are known to be involved in a complex network of signaling pathways that collectively regulate cell proliferation. However, roles of AR in breast cancer development and progression have not been very clearly understood. The proliferation marker Ki-67 has been confirmed as an independent predictive and prognostic factor in early breast cancer. The aims of this study are to identify the clinicopathologic associations and prognostic value of claudin 4 expression in TNBC and to correlate claudin 4 expression with AR status and Ki-67 expression. Paraffin blocks obtained from 56 female patients with triple-negative primary invasive ductal breast carcinomas were analyzed for claudin 4, AR, and Ki-67 immunohistochemical expression. High levels of claudin 4 expression were detected in 66.1% of TNBC cases. There was a significant positive correlation with age, tumor size, grade, nodal status, metastasis, and Ki-67 expression (all P < .05) and negative correlation with AR status (P < .001). Androgen receptor showed positivity in 29 cases (51.78%). There was a statistical negative correlation with the all the studied clinicopathologic parameters, claudin 4 and Ki-67 expression. High claudin 4 expression, negative AR expression, and high Ki-67 index would provide a strong prognostic power to differentiate the patients with worse outcome among TNBC patients. Moreover, target treatment for TNBC cells expressing claudin 4 or AR enriched would be valuable for future therapies.
乳腺癌是女性中最常见的恶性肿瘤，也是全球癌症死亡的主要原因。三阴性乳腺癌（TNBC）是乳腺癌的一种重要表型，在乳腺癌病例中占比相对较小，但在临床、生物学和流行病学层面仍是日益受关注的焦点。紧密连接蛋白是紧密连接的主要成分，仅有少数研究探讨了紧密连接蛋白在乳腺癌尤其是TNBC中的作用。雄激素受体（AR）作为核受体超家族的成员，已知参与了共同调节细胞增殖的复杂信号通路网络。然而，AR在乳腺癌发生发展中的作用尚未完全明确。增殖标志物Ki-67已被确认为早期乳腺癌的独立预测和预后因素。本研究的目的是确定紧密连接蛋白4在TNBC中的临床病理关联和预后价值，并将紧密连接蛋白4的表达与AR状态及Ki-67表达相关联。对56例原发性三阴性浸润性导管乳腺癌女性患者的石蜡块进行紧密连接蛋白4、AR和Ki-67免疫组化表达分析。66.1%的TNBC病例检测到高水平的紧密连接蛋白4表达。其与年龄、肿瘤大小、分级、淋巴结状态、转移及Ki-67表达均呈显著正相关（均P < .05），与AR状态呈负相关（P < .001）。雄激素受体在29例（51.78%）中呈阳性。其与所有研究的临床病理参数、紧密连接蛋白4和Ki-67表达均呈统计学负相关。紧密连接蛋白4高表达、AR阴性表达及Ki-67高指数可为区分TNBC患者中预后较差的患者提供有力的预后评估能力。此外，针对表达紧密连接蛋白4或富集AR的TNBC细胞的靶向治疗对未来治疗具有重要价值。
