Cumulative expression of HIF-1-alpha, Bax, Bcl-xL and P53 in human colorectal cancer

Aims and methods: Hypoxia-inducible factor (HIF-1) which contains oxygen regulated HIF-1alpha subunit maintains cytoprotective defence against hypoxic injury by induction of numerous genes. However, apoptotic regulators such as Bcl-xL, Bax and P53 have not been associated with HIF-1 dependent regulation in immunohistochemical evaluation of human colorectal cancer tumours so far. Thus, we visualised these proteins immunohistochemically and using Spearman's test compared for the first time their expression in regard to different clinicopathological traits in 123 (113 for P53 evaluation) human colorectal cancers. Results: HIF-1alpha correlated with Bcl-xL or Bax in all patients and particularly in node negative and node positive cancers, deeper intramural tumours (pT3+pT4) and adenocarcinomas. There was no significance in a small group of tumours with lesser extent through intestinal walls (pT1+pT2). In addition HIF-1alpha associated with Bcl-xL in mucinous cancers. Moreover, HIF-1alpha correlated with Bcl-xL or Bax in moderately (G2) and poorly differentiated (G3) cancers, rectal and colonic tumours and in different sex and age groups. P53 correlated only with Bax exclusively in younger patients. Conclusions: HIF-1alpha may influence expression of Bax or Bcl-xL, at least indirectly, as correlations between HIF-1alpha and Bax or Bcl-xL occur constantly.