BRCA2 mutation-associated breast cancers exhibit a distinguishing phenotype based on morphology and molecular profiles from tissue microarrays

Bane AL, Beck JC, Bleiweiss I, Buys SS, Catalano E, Daly MB, Giles G, Godwin AK, Hibshoosh H, Hopper JL, John EM, Layfield L, Longacre T, Miron A, Senie R, Southey MC, West DW, Whittemore AS, Wu H, Andrulis IL, O'Malley FP (2007) BRCA2 mutation-associated breast cancers exhibit a distinguishing phenotype based on morphology and molecular profiles from tissue microarrays. Am J Surg Pathol 31:121-128

A distinct morphologic and molecular phenotype has been reported for BRCA1-associated breast cancers; however, the phenotype of BRCA2-associated breast cancers is less certain. To comprehensively characterize BRCA2-associated breast cancers we performed a retrospective case control study using tumors accrued through the Breast Cancer Family Registry. We examined the tumor morphology and hormone receptor status in 157 hereditary breast cancers with germline mutations in BRCA2 and 314 control tumors negative for BRCA1 and BRCA2 mutations that were matched for age and ethnicity. Tissue microarrays were constructed from 64 BRCA2-associated and 185 control tumors. Tissue microarray sections were examined for HER2/neu protein overexpression, p53 status and the expression of basal markers, luminal markers, cyclin D1, bcl2, and MIB1 by immunohistochemistry. The majority of BRCA2-associated tumors and control tumors were invasive ductal, no special-type tumors. In contrast to control tumors, BRCA2-associated cancers were more likely to be high grade (P<0.0001) and="" to="" have="" pushing="" tumor="" margins="" (p="0.0005)." adjusting="" for="" grade,="" brca2-associated="" tumors="" were="" more="" often="" estrogen="" receptor="" positive="" (p="0.008)" and="" exhibited="" a="" luminal="" phenotype="" (p="0.003)." they="" were="" less="" likely="" than="" controls="" to="" express="" the="" basal="" cytokeratin="" ck5="" (p="0.03)" or="" to="" overexpress="" her2/neu="" protein="" (p="0.06)." there="" was="" no="" difference="" in="" p53,="" bcl2,="" mib1,="" or="" cyclin="" d1="" expression="" between="" brca2-associated="" and="" control="" tumors.="" we="" have="" demonstrated,="" in="" the="" largest="" series="" of="" brca2-associated="" breast="" cancers="" studied="" to="" date,="" that="" these="" tumors="" are="" predominantly="" high-grade="" invasive="" ductal="" carcinomas="" of="" no="" special="" type="" and="" they="" demonstrate="" a="" luminal="" phenotype="" despite="" their="" high="" histologic="">