Expression of hypoxia-inducible factor-1α in cervical carcinomas:: Correlation with tumor oxygenation

Purpose: To investigate the relations between hypoxia-inducible factor-1 (HIF-1), tumor oxygenation, and clinical correlates in patients with locally advanced carcinoma of the uterine cervix. Methods and Materials: Biopsies from 42 patients with invasive cervical carcinoma and previous polarographic O-2 measurements were assessed for the expression of HIF-1alpha using digitized microscopic imaging and analysis. Results: The HIF-1alpha expression levels ranged from <0.1% to 10.7% of the total tumor area; the positive staining was localized exclusively to the nuclei. Three distinct arrangement patterns of HIF-1 alpha-positive cells in relation to blood vessels were identified using spatial image mapping: (1) most HIF-1 alpha-positive cells were located within the typical oxygen diffusion distance in tissue (<= 150 mu m to the nearest blood vessel); (2) most HIF-1 alpha-positive cells were located in the vicinity (<= 60 mu m) of the blood vessels; and (3) no apparent spatial relationship was found between HIF-1 alpha-positive cells and blood vessels. A statistically significant association was found between RIF-1 alpha expression and tumor oxygenation (Spearman correlation coefficient = 0.4, p <0.01), as determined with the Eppendorf pO(2) histograph. No correlation was found between the level of HIF-1alpha expression and patient outcome, using disease-free survival as the end point. Conclusion: Our results suggest that HIF-1alpha expression may represent a useful biologic marker for hypoxia in uterine cervical cancer. (C) 2002 Elsevier Science Inc.