Distinguishing medullary carcinoma of the breast from high-grade hormone receptor-negative invasive ductal carcinoma: an immunohistochemical approach.

ABSTRACT

AIMS: Medullary carcinomas (MCs) represent a rare breast cancer subtype associated with a rather favourable prognosis compared with invasive ductal carcinomas (IDCs). Due to histopathological overlap, MCs are frequently misclassified as high-grade IDCs, potentially leading to overtreatment of MCs. Our aim was to establish novel diagnostic markers distinguishing MCs from hormone receptor-negative high-grade IDCs. METHODS AND RESULTS: Sixty-one MCs and 133 hormone receptor-negative IDCs were analysed in a comparative immunohistochemical study. Applied markers included a comprehensive panel of cytokeratins (CKs), vimentin, smooth muscle actin (SMA), p63, p53, cell adhesion molecules [N-CAM (CD56), syndecan-1 (CD138), E-cadherin and P-cadherin] and development associated transcription factors (AP-2 alpha, AP-2 gamma). A significantly higher proportion of IDCs displayed increased expression of CK7, AP-2 alpha and HER2 in contrast to MCs (CK7 91% of IDCs versus 77% of MCs; AP-2 alpha 77% versus 57%; and HER2 26% versus 7%, each P < 0.01). Vice versa, MCs were slightly more frequently positive for SMA and vimentin (P > 0.05). CONCLUSIONS: Hormone receptor-negative high-grade IDCs are significantly associated with luminal differentiation, Her2 and AP-2 alpha overexpression, whereas MCs tend to display myoepithelial features. Markers analysed in this study are of diagnostic value regarding the differential diagnosis of MCs.