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Vascular Endothelial Growth Factor and Soft Tissue Sarcomas: Tumor Expression Correlates With Grade

From the Departments of Surgical Oncology (CC, BE), Pathology (TA-S), and Biostatistics (AR), The Fox Chase Cancer Center, Temple University Medical Center, Philadelphia, Pennsylvania, and the Departments of Surgical Oncology (WGK), and Pathology and Laboratory Medicine (JJB), Roswell Park Cancer Institute, Buffalo, New York.

Correspondence: Address correspondence and reprint requests to: Celia Chao, MD, Department of Surgery, University of Louisville, ACB Building, 2nd Floor, Louisville, KY 40292; Fax: 502-629-3183; E-mail: celia.chao{at}nortonhealthcare.org

Introduction: Vascular endothelial growth factor (VEGF), an endothelial–specific mitogen overexpressed in various epithelial malignancies is thought to be a potent regulator of angiogenesis. We hypothesized that some soft tissue sarcomas, due to their high propensity for hematogenous metastases (1) would overexpress VEGF, (2) that the degree of expression may represent a significant biologic predictor for disease-specific survival, and (3) that recurrent tumor would express as high or higher VEGF compared with the primary tumor.

Methods: Selected paraffin-embedded tissue of surgical specimens from 79 patients with soft tissue sarcomas, treated between 1989 and 1995 were stained with a rabbit polyclonal anti-VEGF antibody at a concentration of 2 µg/ml. Slides were assessed for VEGF expression as high or low by two investigators blinded to the clinicopathologic data. Twelve patients had VEGF expression of their primary tumors, and their recurrent tumors were compared. The Fishers’ exact test assessed for 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 had high VEGF expression. However, VEGF expression was not an independent predictor of either overall or disease-free survival. Tumor grade correlated with VEGF expression significantly. For the low-grade tumors, 7 of 13 expressed 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 immunostaining.

Conclusions: The majority of high-grade soft tissue sarcomas in this study have high intensity VEGF expression. This finding may provide useful information on individual soft tissue sarcomas and offer the basis for therapeutic and biologic targeting in high-risk patients using anti-angiogenesis strategies. However, in our analysis, after accounting for tumor grade, VEGF does not seem to be an independent predictor of clinical outcome.

Key Words: Vascular endothelial growth factor (VEGF) • Soft tissue sarcoma • Immunohistochemistry • Tumor grade

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