Hypoxia inducible factor-1 alpha plays a pivotal role in hepatic metastasis of pancreatic cancer: an immunohistochemical study

Abstract

Background: Hypoxia is an important condition to promote angiogenesis that is essential to tumor progression, including pancreatic ductal adenocarcinoma (PDAC). We evaluated whether the immunohistochemistry for hypoxia inducible factor-1α (HIF-1α) was correlated with hepatic metastases in PDAC.

Methods: We examined the expression of HIF-1α, vascular endothelial growth factor-A (VEGF-A), thymidine phosphorylase (TP) and basic fibroblast growth factor (bFGF) in a total of 100 paraffin-embedded PDAC primary tumors using immunohistochemical staining, and assessed their clinicopathological correlations. We determined microvessel count (MVC) and apoptotic index (AI), and assessed their correlations with hepatic metastases. Student's t-test, the Mann-Whitney U-test, and Spearman correlation coefficients were used to validate the model, and regression analysis was used to test the model.

Results: Hypoxia inducible factor-1α expression induced the expression of multiple angiogenic factors, leading to a higher MVC and a lower AI. HIF-1α expression (P = 0.0087) and angiogenic factors (P = 0.0079) were significantly associated with not only the microvessel status (P = 0.022) but also the high incidence of hepatic metastasis (P = 0.02), resulting in the worse survival of PDAC patients (P < 0.05).

Conclusions: Hypoxia inducible factor-1α plays a pivotal role in hepatic metastasis through its association with the expression of angiogenic factors in PDAC patients. These results may contribute future therapeutic strategies to prevent pancreatic cancer metastasis.

Keywords: Hypoxia inducible factor-1α; Microvessel count; Pancreatic cancer; Thymidine phosphorylase; Vascular endothelial growth factor.