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 alpha (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 H&E immunohistochemistry on paraffin-embedded UM tumor sections using a Tissue Microarray (TMA). The bivariate analysis involving HIF-1α expression and clinicopathological covariates was performed using the Chi-square test. The association of clinicopathological covariates and HIF-1α expression with patient survival was evaluated 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 localization, pigmentation, mitotic figures or microcirculation patterns. Patients with high HIF-1α expression did not showed a reduced survival when compared with patients with low HIF-1α expression (P=0.92).

Conclusions: An increase in HIF-1α expression is significantly associated with proliferative (MIB-1) and vascular (CD31 and VEGF-A) markers, as well as necrosis in UM. However, there is no correlation between high HIF-1α expression and patient survival.

Keywords: 589 melanoma • 452 choroid • 554 immunohistochemistry