Up-regulation and stabilization of HIF-1α in colorectal carcinomas

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates gene expression in critical pathways involved in tumor growth and metastases. In our study we evaluated the expression of HIF-1α transcript and protein by quantitative real time PCR and by immunohistochemistry in a total of 78 colorectal carcinomas (CRCs) and in 8 samples of normal colorectal mucosa in order to identify the impact on prognosis of HIF-1α overexpression in CRCs. Our study demonstrates a significant up-regulation of HIF-1α mRNA as well as a high frequency of the protein immunoreactivity in colorectal cancers compared to normal samples. However, no significant correlation was found between HIF-1α immunohistochemical expression and any of the clinico-pathological parameters evaluated, with the only exception of the positive association between HIF-1α immunoreactivity and the presence of tumor necrosis. Analogously, high levels of HIF-1α mRNA were found to be correlated with a poor grade of tumor differentiation but no other significant association was observed. Despite the careful selection of the tumor samples, our findings do not appear to confirm, for colorectal cancers, the significant association between HIF-1α overexpression and tumor aggressiveness or unfavorable prognosis demonstrated for cancers of other sites. The lack of prognostic impact of HIF-1 in this site could be explained by an intricate interaction between the survival program mediated by HIF-1 and the genetic background of tumors cells in which its activation occurs. © 2007 Elsevier Ltd. All rights reserved.