Hypoxia inducible factor expression in intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (IHCC) is known to be one of the most malignant tumors. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor, which plays a central role in biologic processes under hypoxic conditions. The aim of this study was to elucidate the role of HIF-1 in IHCC.

Thirty-five patients with IHCC who underwent hepatic resection were enrolled in this study. The expression of HIF-1a was determined immunohistochemically and the patients were divided into two groups: HIF-1a positive group (n=22) and HIF-1a negative group (n=13). Clinicopathological variables including prognosis were compared between the two groups. The prognostic factors were investigated by multivariate analysis using Cox's proportional hazard model.

HIF-1a expression correlated significantly with higher stage, and tended to correlate with tumor diameter (>4cm), vessels infiltration and intrahepatic metastasis. The prognosis in HIF-1a positive group was poorer than that in HIF-1a negative group (5-year survival: 62.9% vs. 18.3%). Furthermore, HIF-1a positive expression was identified as an independent prognostic factor for both overall and disease free survival.

The findings suggested that the intratumoral HIF-1a regulated malignant behavior and was a new prognostic indicator of IHCC.