Department of Pathology, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI 02903, USA.
Hum Pathol. 2013 Dec;44(12):2743-50. doi: 10.1016/j.humpath.2013.07.021.
Calretinin, a calcium-binding protein, is a widely used marker for mesothelial differentiation. There is accumulating evidence of calretinin expression in epithelial and mesenchymal malignancies, as well. The objectives of this study were to (1) further delineate the expression of calretinin in grade 3 breast carcinomas in the context of molecular subtypes and (2) identify the impact of calretinin expression on overall and disease-free survival. On the basis of immunohistochemical expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 (HER2), cytokeratin 5/6, and epidermal growth factor receptor, 214 grade 3 invasive ductal carcinomas were stratified into 36 luminal A, 63 luminal B, 24 HER2 positive, 81 basal-like (including 13 metaplastic carcinomas), and 10 unclassified. Tissue microarrays were analyzed for immunohistochemical expression of calretinin. High-level calretinin expression was identified in a significant proportion of basal-like (54.3%), HER2 (33.3%), and unclassified (30%) tumors. In contrast, luminal A and B subtypes demonstrated high-level calretinin expression in only 11.1% and 12.7%, respectively (P < .0001). Within the basal-like group, 38.5% of the metaplastic carcinomas demonstrated high-level expression, associated predominantly with the epithelial component and squamous metaplasia. High-level calretinin expression was strongly associated with decreased overall survival in the entire cohort of grade 3 cancer (P = .0096) and in the basal-like group (P = .039). Multivariate analysis revealed that both tumor stage and high-level calretinin expression were independent predictors of overall survival (P = .0002 and P = .0023, respectively). In conclusion, high-level calretinin expression is most common in grade 3 tumors with a basal-like phenotype and is associated with poor overall survival.
钙结合蛋白 calretinin 是间皮分化的广泛应用标志物。越来越多的证据表明 calretinin 在上皮和间充质恶性肿瘤中也有表达。本研究的目的是：(1)进一步描述 calretinin 在分子亚型 3 级乳腺癌中的表达情况；(2)确定 calretinin 表达对总生存和无病生存的影响。根据雌激素受体、孕激素受体、人表皮生长因子受体 2 (HER2)、细胞角蛋白 5/6 和表皮生长因子受体的免疫组织化学表达，将 214 例 3 级浸润性导管癌分为 36 例 luminal A、63 例 luminal B、24 例 HER2 阳性、81 例基底样（包括 13 例化生癌）和 10 例未分类。对组织微阵列进行 calretinin 的免疫组织化学表达分析。基底样（54.3%）、HER2（33.3%）和未分类（30%）肿瘤中有相当比例显示高水平的 calretinin 表达。相比之下，luminal A 和 B 亚型的高水平 calretinin 表达率分别仅为 11.1%和 12.7%（P<0.0001）。在基底样组中，38.5%的化生癌显示高水平表达，主要与上皮成分和鳞状化生有关。高水平的 calretinin 表达与整个 3 级癌症队列（P=0.0096）和基底样组（P=0.039）的总生存时间缩短密切相关。多变量分析显示，肿瘤分期和高水平的 calretinin 表达均为总生存的独立预测因素（P=0.0002 和 P=0.0023）。结论：高水平的 calretinin 表达最常见于具有基底样表型的 3 级肿瘤，与总生存不良相关。
