The role of hypoxic-inducible factor (HIF1α) and aldolaseC protein in endometrial carcinogenesis: a retrospective study of 279 patients

Objectives: Hypoxia-inducible factor (HIF1 alpha) plays an integral role in response to hypoxia, controlling dozens of target genes including aldolaseC (ALDC), an important enzyme in the glycolytic pathway. It also induces angiogenesis, allowing survival and proliferation of cancer cells. The aims of our study were to evaluate the expressions of HIF1 alpha and ALDC in patients with endometrial cancer (EC) and define their association with disease outcome and to determine the existence of an association between HIF1 alpha and ALDC proteins. Design: This is a population-based retrospective cohort study using the gynaecological-oncology database. The authors identified all women with EC with adequate follow-up. Immunohistochemistry using antibodies to ALDC and HIF1 alpha was performed on paraffin-embedded tissue from 279 patients. To test the association between ALDC /HIF1 alpha protein using immunohistochemistry (IHC) (positive and negative) and the clinical parameters, Fisher's exact test was performed for categorical parameters and the logistic regression model was used for continuous ones. Pearson correlation was used to check the association of IHC between ALDC and HIF1 alpha. Setting: Academic referral centre. Participants: Women with EC from 2000 to 2010 obtained from the gynaecological-oncology database. Outcome measures: The disease outcome is defined by alive with no evidence of disease versus all other outcomes. Results: ALDC and HIF1 alpha were overexpressed in the vast majority of EC cases (78% and 76%, respectively). There was a strong positive association between HIF1 alpha and ALDC (p=0.0017). There was a significant association between ALDC and depth of myometrial invasion (p=0.0438), and between HIF1 alpha and tumour grade (p=0.0231) and tumour subtype (p=0.018). However, there was no association between neither ALDC nor HIF1 alpha and disease status. Conclusions: ALDC and HIF1 alpha play an important role in endometrial carcinogenesis. Their expression by the majority of EC makes inhibition of HIF1 alpha a very attractive therapeutic option for treating patients with EC and we suggest that it will be prospectively validated in future studies.