Calretinin expression in high-grade invasive ductal carcinoma of the breast is associated with basal-like subtype and unfavorable prognosis

Abstract

Calretinin, a calcium-binding protein, is a widely utilized marker for mesothelial differentiation. There is accumulating evidence of calretinin expression in epithelial and mesenchymal malignancies as well. The objectives of this study were 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 (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), CK5/6 and epidermal growth factor receptor (EGFR), 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<0.0001). 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=0.0096) and in the basal-like group (P=0.039). Multivariate analysis revealed that both tumor stage and high-level calretinin expression were independent predictors of overall survival (P=0.0002 and P=0.0023, 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.

Clinicopathologic Features of Breast Carcinomas Classified by Biomarkers and Correlation with Microvessel Density and VEGF Expression: A Study from Thailand

“…More cases should be studied to find the clinical significance of the TNB and TNN and any biomarkers that could predict the clinical outcome other than the ones that we used to classify these two subtypes. Recently calretinin expression had been found to correlate with poor clinical outcome in TNB subtype (Taliano et al, 2013). We did not study this marker in the current study.…”

Serum calretinin as an independent predictor for platinum resistance and prognosis in ovarian cancer

“…Moreover, global gene expression analysis in ovarian/peritoneal serous carcinoma (O/P‐SC) versus diffuse peritoneal malignant mesothelioma (DMPM) revealed that CRT was overexpressed in DMPM but not in O/P‐SC, suggesting that CRT could be (along a potential gene‐expression signature) a marker for differentiating DMPM from O/P‐SC . In breast cancer, for comparison, strong CRT expression was predominantly observed in high‐grade tumors with basal‐like phenotypes and paralleled poor prognosis . Moreover, an alternatively spliced form of CRT (CRT‐22k) was detected in serum of breast cancer patients…”

“…27 In breast cancer, for comparison, strong CRT expression was predominantly observed in high-grade tumors with basal-like phenotypes and paralleled poor prognosis. 28,29 Moreover, an alternatively spliced form of CRT (CRT-22k) was detected in serum of breast cancer patients. 30 Considering that CRT is also highly expressed in mesothelial cells of the peritoneum, 15,16 it is alternatively possible that elevated sCRT in advanced ovarian cancer patients is related to the tumor microenvironment within peritoneal metastases.…”

Solid papillary carcinoma with reverse polarity of the breast harbors specific morphologic, immunohistochemical and molecular profile in comparison with other benign or malignant papillary lesions of the breast: a comparative study of 9 additional cases

“…Calretinin expression has already been reported in normal breast tissues and breast carcinoma [25]. In three studies, this marker was associated to breast carcinoma of worse prognosis, especially of basal-like phenotype [26][27][28].…”