Evaluation of relationship between HIF-1α immunoreactivity and stage, grade, angiogenic profile and proliferative index in bladder urothelial carcinomas

Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a critical regulatory protein of cellular response to hypoxia. In this study, we evaluated the relationship of HIF-1 alpha with clinicopathologic parameters such as tumor stage and grade, as well as angiogenic profile and proliferation index. The immunoreactivity of HIF-1 alpha was assessed in 70 cases of primary bladder urothelial carcinoma. Vascular endothelial growth factor (VEGF) and microvessel density (MVD) were used to evaluate the angiogenic profile. MVD was calculated by immunohistochemical staining of endothelial cells with CD34. Proliferation index was determined by the percentage of Ki-67 nuclear staining in tumor cells. There was a significant relationship between HIF-1 alpha immunoreactivity and stage, as well as histologic grade of the tumor (P < 0.001). HIF-1 alpha immunoreactivity was also closely related to VEGF expression (P < 0.001), MVD (P = 0.002) and proliferation index (P < 0.001). VEGF, MVD and proliferation index were found to be closely related to tumor stage and histologic grade. There was no correlation between HIF-1 alpha immunoreactivity and lamina propria (P = 0.13), muscularis propria (P = 0.009) or vascular invasion (P = 0.1). In this study, HIF-1 alpha expression was found to be closely related to prognostic parameters in bladder urothelial carcinoma. For this reason, it may be a useful marker to determine the prognosis and to choose the appropriate treatment modality.