Vascular integrin α(v)β₃: A new prognostic indicator in breast cancer

Blood vessel density is a prognostic indicator of multiple tumor types. Recently, it has been established that tumor-associated blood vessels express elevated levels of integrin α(v)β₃. In fact, there is evidence that integrin α(v)β₃ identifies the most proliferative endothelial cells within hut man breast carcinomas. Therefore, we evaluated breast cancer tissue in terms of both blood vessel density and α(v)β₃ expression. We found that the antibody LM609 to integrin α(v)β₃ preferentially stains the blood vessels of small caliber. Furthermore, comparative studies between LM609 and anti-CD31 antibodies on normal breast indicate that very low and weak expression of integrin α(v)β₃ was found on vessels within normal tissue, whereas CD31 antigen was expressed in almost all vasculature. Indeed, expression of integrin α(v)β₃ was significantly higher in tumors of patients with metastasis than in those without metastasis. In a series of 197 consecutive patients with invasive breast cancer and long follow-up, vascular expression of integrin α(v)β₃ in tumor vascular 'hot spots' was found to be the most significant prognostic factor predictive of relapse-free survival in both node-negative and node-positive patients. These findings support the contention that angiogenesis plays a critical role in breast cancer progression and suggest that integrin α(v)β₃ is an endothelial cell marker with significant prognostic value and potential usefulness as a target for specific antiangiogenic therapy.