Plausible linkage of hypoxia-inducible factor (HIF) in uterine endometrial cancers

Objective: Angiogenesis is essential for the development, growth and advancement of solid tumors. Angiogenesis is induced by hypoxia with the angiogenic transcription factor hypoxia-inducible factor (HIF). This prompted us to study the clinical implications of HIF relative to angiogenesis in uterine endometrial cancers. Methods: Sixty patients underwent curative resection for uterine endometrial cancers. In the tissue of 60 uterine endometrial cancers, HIF-1 alpha, HIF-2 alpha and HIF-1 beta mRNA levels, and the ratio of angiopoietin (Ang)-2 to Ang-1 (Ang-2/Ang-1) mRNA levels were determined by RT real-time PCR; histochemical scores and localization of HIF-1 alpha were determined by immunohistochemistry. Levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), thymidine phosphorylase (TP) and interleukin-8 (IL-8) were determined by enzyme immunoassay. Results: In stage I uterine endometrial cancers, HIF-1 alpha histochemical scores and mRNA levels significantly increased with myometrial invasion of uterine endometrial cancers. HIF-1 alpha histochemical scores and mRNA levels correlated with the levels of Ang-2/Ang-1 and IL-8. Conclusion: The angiogenic mediator HIF-1 alpha, linked to Angs and IL-8, might work on angiogenesis with myometrial invasion of cancer cells in uterine endometrial cancers.