Primary tumor vascularity, HIF-1α and VEGF expression in vulvar squamous cell carcinomas: their relationships with clinicopathological characteristics and prognostic impact.

ABSTRACT

BACKGROUND: Increased vascularity is a crucial event in the tumor progression and has prognostic significance in various cancers. However, the ultimate role of angiogenesis in the pathogenesis and clinical outcome of vulvar carcinoma patients is still not settled. METHODS: Tumor vascularity using CD34 stained slides measured by Chalkley counting method as well as hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) immunoexpression was examined in 158 vulvar squamous cell carcinomas. Associations between vascular Chalkley count, HIF-1α and VEGF expression and clinicopathological factors and clinical outcome were evaluated. RESULTS: High CD34 Chalkley count was found to correlate with larger tumor diameter (P = 0.002), deep invasion (P < 0.001) and HIF-1α (P = 0.04), whereas high VEGF expression correlate significantly with poor tumor differentiation (P = 0.007). No significant association between CD34 Chalkley counts and VEGF expression and disease-specific survival was observed. High HIF-1α expression showed better disease specific survival in both univariate and multivariate analyses (P = 0.001). CONCLUSIONS: A significant association between high tumor vascularity and larger tumor size as well as deeper tumor invasion suggests an important role of angiogenesis in the growth and progression of vulvar carcinomas. HIF-1α expression in vulvar carcinomas was a statistically independent prognostic factor.