Tumor VEGF expression correlates with tumor stage and identifies prognostically different groups in patients with clear cell renal cell carcinoma

Objectives: Vascular endothelial growth factor (VEGF) is a potent inducer of tumor angiogenesis and represents the key element in the pathogenesis of clear cell renal cell carcinoma (ccRCC). The aim of this study was to investigate the use of tumor VEGF expression as a parameter to identify tumor stage and prognostically different patient groups.

Methods and materials: We retrospectively collected clinical data of 137 patients treated with partial or radical nephrectomy at our institutions for organ-confined, locally advanced, and metastatic ccRCCs between 1984 and 2013. Tumor cell VEGF immunohistochemical expression was compared with pathological and clinical features including age, sex, tumor stage, and Fuhrman grade. Comparison of VEGF expression levels between tumor stages was performed via Kruskal-Wallis nonparametric test. Survival analysis was conducted via Kaplan-Meier product-limit method, and Mantel-Haenszel log-rank test was employed to compare survival among groups.

Results: Median age at diagnosis was 61 years (range: 33-85 y). Tumor stage was pT1N0M0 in 67 patients (49%), pT2N0M0 in 5 (4%), and pT3N0M0 in 25 (18%), while 40 patients (29%) had metastatic tumors at diagnosis. Fuhrman nuclear grade was G1 in 22 patients (16%), G2 in 60 (44%), G3 in 33 (24%), G4 in 13 patients (9%), and unknown in 9 patients. Tumor VEGF was differentially expressed among different stages (P<0.001) and in low (G1-2) and high (G3-4) Fuhrman grade tumors (P<0.001). No significant differences were found when stratifying by sex (P = 0.06) or age (P = 0.29). Median overall survival (OS) from partial or radical nephrectomy was 161 months (range: 1-366). We observed a significantly longer OS in patients with low (<25%) vs. high (>25%) VEGF expression levels (median OS 206 vs. 65 mo, P<0.001).

Conclusions: Our data show that tumor cell VEGF expression is significantly associated with tumor stage and Fuhrman grade and is able to predict patient outcome, suggesting a potential use of this parameter in identifying prognostically different patients with ccRCC.