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

Abstract 

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.

Biopsies from 42 patients with invasive cervical carcinoma and previous polarographic O₂ measurements were assessed for the expression of HIF-1α using digitized microscopic imaging and analysis.

The HIF-1α 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-1α-positive cells in relation to blood vessels were identified using spatial image mapping: (1) most HIF-1α-positive cells were located within the typical oxygen diffusion distance in tissue (≤150 μm to the nearest blood vessel); (2) most HIF-1α-positive cells were located in the vicinity (≤60 μm) of the blood vessels; and (3) no apparent spatial relationship was found between HIF-1α-positive cells and blood vessels. A statistically significant association was found between HIF-1α expression and tumor oxygenation (Spearman correlation coefficient = 0.4, p <0.01), as determined with the Eppendorf pO₂ histograph. No correlation was found between the level of HIF-1α expression and patient outcome, using disease-free survival as the end point.

Our results suggest that HIF-1α expression may represent a useful biologic marker for hypoxia in uterine cervical cancer.

Keywords:  Image analysis, Hypoxia, HIF-1α, Eppendorf pO₂ histograph, Cervical carcinoma