title: 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 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.
authors.affiliation: Department of Pathology, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI 02903, USA. Electronic address: rtaliano@lifespan.org.
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Taliano
authors.forename: Shaolei
authors.initials: S
authors.lastname: Lu
authors.forename: Kamaljeet
authors.initials: K
authors.lastname: Singh
authors.forename: Shamlal
authors.initials: S
authors.lastname: Mangray
authors.forename: Rose
authors.initials: R
authors.lastname: Tavares
authors.forename: Lelia
authors.initials: L
authors.lastname: Noble
authors.forename: Murray B
authors.initials: MB
authors.lastname: Resnick
authors.forename: Evgeny
authors.initials: E
authors.lastname: Yakirevich
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001940:Breast / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D064032:Calbindin 2 / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D015996:Survival Rate
chemical_list: D064032:Calbindin 2; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone
keywords: Basal-like; Breast; Calretinin; Carcinoma; Immunohistochemisty