VASCULAR INTEGRIN ALPHA(V)BETA(3) - 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 vessel s express elevated levels of integrin alpha(v)beta(3). In fact, there is evidence that integrin alpha(v)beta(3) identifies the most prolifer ative endothelial cells within human breast carcinomas. Therefore, we evaluated breast cancer tissue in terms of both blood vessel density a nd alpha(v)beta(3) expression. We found that the antibody LM609 to int egrin alpha(v)beta(3) 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 expressio n of integrin alpha(v)beta(3) was found on vessels within normal tissu e, whereas CD31 antigen was expressed in almost all vasculature, Indee d, expression of integrin alpha(v)beta(3) was significantly higher in tumors of patients with metastasis than in those without metastasis, I n a series of 197 consecutive patients with invasive breast cancer and long follow-up, vascular expression of integrin alpha(v)beta(3) in tu mor vascular ''hot spots'' was found to be the most significant progno stic 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 s uggest that integrin alpha(v)beta(3) is an endothelial cell marker wit h significant prognostic value and potential usefulness as a target fo r specific antiangiogenic therapy.