Vascular endothelial growth factor expression in the basal subtype of breast carcinoma

The recognition of subtypes of breast carcinomas based on their molecular features has brought new perspectives in breast cancer research. Some key regulators of angiogenesis and tumor infiltration were evaluated in breast carcinomas of basal phenotype (cytokeratin [CK]5+). Immunohistochemical analysis with 14 primary antibodies was performed in 100 formalin-fixed, paraffin-embedded samples of invasive ductal carcinomas. CK5 correlated with indicators of poor outcome, including precocious age, high histologic grade, lymph node positivity, advanced pathologic stage, negativity for hormonal receptors, and a high proliferative rate (Ki-67 labeling index). CK5 also correlated with vascular endothelial growth factor (VEGF) expression but not with the microvessel density. Considering that VEGF-overexpressing neoplastic mammary cells display increased proliferative activity in vitro regardless of the angiogenic effect of VEGF, the differential expression of VEGF might contribute to the more aggressive behavior of these neoplasms. CK5 correlated with tissue inhibitor of metalloproteinase (TIMP)-1, but not matrix metalloproteinase (MMP)-1, MMP-2, extracellular matrix metalloproteinase inducer, TIMP-2 or plasminogen activator inhibitor, indicating that antiproteolytic stimuli might be preponderant in these neoplasms.