Inference of the Basal Epithelial Phenotype in Breast Carcinoma from Differential Marker Expression, Using Tissue Microarrays in Triple Negative Breast Cancer and Women Younger than 35

Abstract

Basal-cell phenotype breast carcinoma has been associated with high-grade and metaplastic morphology, expression of basal-type cytokeratins, uniform negativity for ER and HER2, and decreased overall survival. Breast cancers occurring in young women are usually T2 disease at presentation, high-grade and of poor prognosis. We compared two groups of breast cancers, (a) ER-, PR-, HER2- (triple negative) [TNBrCa] and (b) non-triple negative breast cancers (non-TNBrCa) occurring in women under 35, using tissue microarray technology to characterize expression of the basal/myoepithelial cytokeratins (CK5/6, CK7, and CK14), luminal cytokeratins (CK8, CK18, and CK19), EGFR, p-cadherin, c-kit, p63, and p53. We also sought to identify characteristic histomorphologic features indicative of basal-like phenotype. The triple negative group showed preferential staining versus the age <35 group for CK5/6 (22% versus 4% p = 0.05), CK14 (44% versus 15%, p = 0.013), EGFR (83% versus 24%, p < 0.0001) and c-kit (19% versus 0% p = 0.026). Conversely, non-TNBrCa in women younger than 35 demonstrated increased expression of the luminal CK8 (92% versus 60%) compared with the triple negative patients (p = 0.006). The TNBrCa have characteristic histologic features including higher tumor grade, pushing tumor border, geographic necrosis, syncytial growth pattern, brisk mitotic activity, lack of/minimal in situ component, medullary-like and metaplastic differentiation. Invasive carcinomas in women younger than 35 usually have an associated in situ component, prominent nucleoli, central acellular fibrotic zone, and infiltrative tumor border. Triple negativity for ER/PR/HER2 coupled with EGFR, c-kit, and basal/myoepithelial cytokeratins (CK5/6, CK14) expression, and distinctive histomorphologic features predict morphology consistent with basal-cell phenotype.