Expression of hypoxia-inducible factor-1 alpha is associated with an unfavorable prognosis in non-small cell lung cancer

Abstract

7147 Background: Hypoxia-inducible factor (HIF) -1alpha is a transcription factor that mediates adaptive responses of human cells in tissue hypoxia. HIF-1alpha activates various factors supporting tumor growth and progression. HIF-1alpha expression in patients with non-small cell lung cancer (NSCLC), however, has not been well studied. The aim of this study was to determine the expression of HIF-1alpha protein and its relation to clinicopathologic features and prognosis of patients with NSCLC. Methods: We studied retrospectively expression of HIF-1alpha protein in 139 patients with NSCLC by immunohistochemistry. Nuclear expression of HIF-1alpha was measured by observing 1000 cancer cells. The percentage of positive cells was rated as follows: negative expression, cases with <10% positive cells; weak expression, 10–50% positive cells; moderate expression, 50.1–80% positive cells; and strong expression, cases with 80% positive cells. Expression of HIF-1alpha was compared in relation to clinicopathologic findings. Results: HIF-1alpha expression ranged from 0 to 98.8% with a mean value of 41.8%. Forty-two patients (30.2%) showed negative expression, 37 patients (26.6%) showed weak expression, 32 patients (23%) showed moderate expression, and 28 patients (20.1%) showed strong expression. HIF-1alpha expression showed significant correlation with histology, pT status, or pathological stage (p=0.0012, p=0.0097, p=0.008, respectively). Five-year survival rates of negative expression group, weak expression group, moderate expression group and strong expression were 80.2%, 68.4%, 40%, and 20.5%, respectively (p<0.0001, log-rank test). A multivariate analysis of survival time by the stepwise procedure revealed that pathological stage and HIF-1alpha expression were statistically significant prognostic factors (p<0.0001, p=0.0002, respectively). Conclusions: This study shows that HIF-1alpha may be an independent prognostic factor, which can indicate the subsets of patients with poor prognosis, in patients with NSCLC who underwent surgical resection. No significant financial relationships to disclose.