Calretinin Expression in Poorly Differentiated Breast Carcinomas with an Emphasis on the Basal-Like Subtype
K Singh, H Sidhu, S Mangray, R Tavares, L Noble, M Resnick, R DeLellis, E Yakerewich. Brown University, Providence, RI
Background: Basal-like subtype of breast cancer was identified by gene expression profiling. These tumors express basal cytokeratins and epidermal growth factor receptor (EGFR), but lack estrogen receptor (ER), progesterone receptor (PR) and HER2. Because this subtype has a poor prognosis, there has been a consistent effort to refine its morphological and immunophenotypic features. Calretinin is one of the calcium binding protein. It is expressed in a variety of normal tissues and several malignancies. Our goal was to investigate the expression pattern and diagnostic utility of calretinin in the basal-like subtype of breast carcinoma.
Design: Paraffin embedded microarray tissue from 248 consecutive poorly differentiated invasive ductal carcinomas was analyzed for expression of calretinin(mouse monoclonal antibody, clone Z11-E3, Zymed). On the basis of expression of ER, PR, HER2, cytokeratin-5/6 and EGFR the cases were stratified into luminal (ER+/PR+), HER2 positive (ER-/PR-/HER2+), and basal-like (ER-/PR-/HER2-/CK5/6+ and /or EGFR+) subtypes. The extent and intensity of calretinin expression were scored semiquantitatively using a combined score on a scale of 0-3+.
Results: The cases were stratified into 71 luminal, 71 HER2, and 94 basal-like. Positive calretinin staining was characterized by the presence of both nuclear and cytoplasmic reactivity. Of the total 248 poorly differentiated carcinomas calretinin expression was seen in 90 (36%) cases. Calretinin positivity was found in a significant proportion of the basal-like cancers (55/94,59%). In this group, the majority of positive cases (48 of 55, 87%) demonstrated strong (2+, 3+) calretinin positivity. In contrast, luminal and HER2 subtypes showed calretinin expression in only 24% & 25% of cases, respectively (p<0.001). There was a significant positive association of expression of calretinin with cytokeratin 5/6 and EGFR (p<0.001).
|Tumor subtype||Frequency||Calretinin positive||Strong calretinin positive (2+-3+)|