Prognostic role of tumor necrosis, microvessel density, vascular endothelial growth factor and hypoxia inducible factor-1 alpha in patients with clear cell renal carcinoma after radical nephrectomy in a long term follow-up

Angiogenesis is a critical step in the growth, invasive progression and metastatic spread of solid tumors. We investigated the importance of tumor necrosis, and microvessel density (MVD), vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1alpha (HIF-1alpha) immunohistochemical expression in a large series of clear cell renal carcinomas treated with radical nephrectomy and assessed the prognostic value of their expression in terms of patient survival at long-term followup. Fifty patients with clear cell RCC were examined. The features considered when evaluating the patients were age, tumor size and grade, intratumoral vascular and renal capsula invasion, histological necrosis, and MVD, vascular and tumoral cell VEGF, and vascular, tumoral cytoplasmic and nuclear HIF-1alpha expression on the histologic specimens. All considered parameters were correlated with patient specific survival. Mean age was 62.06 +/- 6.8 years. Median follow-up was 191.66 months; median survival was 120.86 months. Twenty-one patients developed metastases in the follow-up. Tumor necrosis, microvascular invasion and renal capsula infiltration are more likely to occur in high stage and grade RCC; cytoplasmic HIF-1alpha is highly expressed in high grade RCC. Survival is dependent upon tumor stage and grade, the presence of intratumoral vascular invasion and capsular infiltration, and tumor necrosis; MVD also resulted as being an important prognostic factor. VEGF and HIF-1alpha correlate with prognosis in high stage tumors where VEGF is the most important independent prognostic factor for cancer specific death. The histological and immunohistochemical parameters considered in our study can influence disease recurrence and survival in RCC.