Vascular endothelial growth factor and soft tissue sarcomas: Tumor expression correlates with grade

Introduction: Vascular endothelial growth factor (VEGF), an endothelial-spe cific mitogen overexpressed in various epithelial malignancies is thought t o be a potent regulator of angiogenesis. We hypothesized that some soft tis sue sarcomas, due to their high propensity for hematogenous metastases (1) would overexpress VEGF, (2) that the degree of expression may represent a s ignificant biologic predictor for disease-specific survival, and (3) that r ecurrent tumor would express as high or higher VEGF compared with the prima ry tumor. Methods: Selected paraffin-embedded tissue of surgical specimens from 79 pa tients with soft tissue sarcomas, treated between 1989 and 1995 were staine d with a rabbit polyclonal anti-VEGF antibody at a concentration of 2 mug/m l. Slides were assessed for VEGF expression os high or low by two investiga tors blinded to the clinicopathologic data. Twelve patients had VEGF expres sion of their primary tumors, and their recurrent tumors were compared. The Fishers' exact test assessed fur differences in VEGF expression; survival analyses were performed according to the methods of Kaplan and Meier. Results: Seventy-eight percent (29 of 37) of patients who died of disease h ad high VEGF expression. However, VEGF expression was not an independent pr edictor of either overall or disease-free survival. Tumor grade correlated with VEGF expression significantly. For the low-grade tumors, 7 of 13 expre ssed low VEGF, whereas for high-grade tumors, 53 of 66 expressed high VEGF (P = .016). Seven of the 12 paired tumor samples expressed identical VEGF i mmunostaining. Conclusions: The majority of high-grade soft tissue sarcomas in this study have high intensity VEGF expression. This finding may provide useful inform ation on individual soft tissue sarcomas and offer the basis for therapeuti c and biologic targeting in high-risk patients using anti-angiogenesis stra tegies. However, in our analysis, after accounting for tumor grade, VEGF do es not seem to be an independent predictor of clinical outcome.