Increased HIF-1α expression correlates with cell proliferation and vascular markers CD31 and VEGF-A in uveal melanoma.

ABSTRACT

PURPOSE: Overexpression of hypoxia inducible factor-1 α (HIF-1α) has been found in several cancers and is thought to correlate with aggressive disease. The purpose of our study was to investigate the influence of HIF-1α on clinical outcome in uveal melanoma (UM) along with proliferative (MIB-1) and vascular (CD31, VEGF-A) markers. METHODS: A retrospective analysis was carried out on UM tumors from 88 patients. HIF-1α, MIB-1, CD31, and VEGF-A expression, as well as necrosis, were assessed by immunohistochemistry and hematoxylin/eosin on paraffin-embedded UM tumor sections by using a tissue microarray. The bivariate analysis involving HIF-1α expression and clinicopathologic covariates was performed by using the χ(2) test. The association of clinicopathologic covariates and HIF-1α expression with patient survival was evaluated by using the Kaplan-Meier approach and Cox proportional-hazards regression analysis. RESULTS: Among our study population, 56 patients (63.6%) had high levels of HIF-1α expression. High expression of HIF-1α was associated with high expression of MIB-1 (P = 0.04), CD31 (P = 0.03), and VEGF-A (P < 0.0001), as well as necrosis (P = 0.04). However, high HIF-1α expression was not correlated with cell type, largest macroscopic tumor dimension or thickness, anterior margin, pigmentation, or mitotic figures. Patients with high HIF-1α expression did not show a reduced survival when compared to patients with low HIF-1α expression (P = 0.92). Finally, HIF-1α expression was not increased after irradiation. CONCLUSIONS: An increase in HIF-1α expression was significantly associated with proliferative (MIB-1) and vascular (CD31 and VEGF-A) markers, as well as necrosis, in UM. However, there was no correlation between high HIF-1α expression and patient survival.