Abstract：
Cytokeratin 15 (CK15) has been described as a stem cell marker in human organs and its expression is seen in breast tissue. CK15 expression is associated with aggressive features in endometrial and oesophageal cancers, but data on the breast are lacking. This study aims to investigate the clinicopathological associations and prognostic significance of CK15 in breast carcinomas. A multi-institute cohort of breast carcinomas were retrieved. Clinicopathological and outcome data were obtained and compared with immunohistochemical expression CK15 and a panel of biomarkers. In total, 1,476 cases were included, with an expression rate of 3.5%, preferentially expressed in luminal subtypes (p=0.024), with luminal B carcinomas being the highest (4.7%), as opposed to basal-like (1%) and HER2-overexpressed carcinomas (0%). Except for nodal stage (p=0.013) and nodal metastasis (p=0.048), oestrogen (p=0.035) and progesterone receptor (p=0.001) positivity, there were no associations with other clinicopathological parameters. A trend was observed with shorter breast cancer specific survival (BCSS) in CK15-positive luminal B carcinomas (p=0.062). On further subgroup multivariate analysis of luminal B HER2-negative carcinomas, CK15 expression exhibited robust correlation with shorter BCSS (HR=9.004, p=0.001) and disease-free survival (HR=7.085, p<0.001). Restricted to luminal breast carcinomas, specifically luminal B HER2-negative, CK15 is demonstrated to be a robust independent predictor of higher risk of recurrence and shorter survival, with potential as a clinical prognostic marker and an exclusive stem cell marker for this subgroup of carcinomas.
摘要：
细胞角蛋白15（CK15）已被描述为人体器官中的干细胞标志物，其表达在乳腺组织中可见。CK15表达与子宫内膜癌和食管癌的侵袭性特征相关，但是缺乏乳房数据。本研究旨在探讨CK15在乳腺癌中的临床病理相关性和预后意义。检索了一个多机构的乳腺癌队列。获得临床病理和结果数据，并与免疫组织化学表达CK15和一组生物标志物进行比较。总的来说,包括1476例，表达率为3.5%，在腔亚型中优先表达（p=0.024），其中管腔B癌最高（4.7％），与基底样癌（1％）和HER2过表达癌（0％）相反。除淋巴结分期（p=0.013）和淋巴结转移（p=0.048）外，雌激素（p=0.035）和孕激素受体（p=0.001）阳性，与其他临床病理参数无相关性.在CK15阳性管腔B癌中，观察到乳腺癌特异性生存期（BCSS）较短的趋势（p=0.062）。在腔内BHER2阴性癌的进一步亚组多变量分析中，CK15表达与较短的BCSS（HR=9.004，p=0.001）和无病生存期（HR=7.085，p<0.001）具有强相关性。限于管腔内乳腺癌，特别是腔内BHER2阴性，CK15被证明是较高复发风险和较短生存期的可靠独立预测因子。具有潜在的临床预后标志物和该亚组癌症的唯一干细胞标志物。
