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 alpha(v)beta3. In fact, there is evidence that
integrin alpha(v)beta3 identifies the most proliferative endothelial cells within human
breast carcinomas. Therefore, we evaluated
breast cancer tissue in terms of both blood vessel density and alpha(v)beta3 expression. We found that the antibody LM609 to
integrin alpha(v)beta3 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 alpha(v)beta3 was found on vessels within normal tissue, whereas
CD31 antigen was expressed in almost all vasculature. Indeed, expression of
integrin alpha(v)beta3 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 alpha(v)beta3 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 alpha(v)beta3 is an endothelial cell marker with significant prognostic value and potential usefulness as a target for specific antiangiogenic
therapy.