Primary tumor vascularity in esophagus cancer. CD34 and HIF1-α expression correlate with tumor progression

Abstract

Objective: Hypoxia inducible factor α (HIF1-α) is a key protein regulating the response of a variety of genes and pathways, including angiogenesis, to hypoxic stimuli. High vascularity in various carcinomas correlates with invasion and metastasis. Assessment of primary tumor vascularity and HIF1-α expression in esophageal carcinomas was an objective of this study. Methods: The vascularity in esophageal carcinomas (n=52) was quantified by Chalkley method on CD34 immunostained sections. HIF1-α expression was examined by immunohistochemistry. The relationships between CD34 Chalkley count, HIF1-α and various clinico-pathological characteristics with clinical outcome were evaluated. Results: High HIF1-α expression in squamous cell carcinoma (SCC) was significantly associated with the T3-4 group (p=0.02). A higher percentage of SCC with high HIF1-α expression compared to its expression in adenocarcinoma (AC) (p=0.005) was observed. In the SCC group, high CD34 Chalkley count and high HIF1-α expression implied a significantly reduced survival (p=0.003 and p=0.001). No such significant association was found in the AC group. Conclusions: HIF1-α expression is different in two separate tumor microenvironments: SCCs and ACs of the esophagus. This suggests that different mechanisms may be involved in HIF1-α expression- and activity between the two histological types of esophageal carcinoma.