Evaluation of VEGF A Expression and Microvascular Density As Prognostic Factors in Extrahepatic Cholangiocarcinoma

Objectives: Angiogenesis is essential for tumor growth and metastasis. An association between microvessel density, a measure of tumor angiogenesis, and conventional prognostic variables has been shown for many different tumor entities. In extrahepatic cholangiocarcinoma, the VEGF expression and microvessel density have rarely been investigated.

Methods: Paraffin-embedded specimens from 51 resected adenocarcinomas of the extrahepatic bile duct were immunostained for vascular endothelial growth factor A (VEGF A) and CD 34 to evaluate the microvessel density (MVD). VEGF A staining was evaluated by combining intensity and percentage of positive tumor cells, as low (expression equal or below the median), or high (above the median). Microvessel density was assessed using a method published by Weidner et al.

Results: Median disease free survival (DFS) of the study group was 12.5 months (range, 1-66.3 months). DFS was calculated in the 39 patients with complete resection. It was significantly better in patients with low microvessel density than DFS in patients with high microvessel density (33 months (range, 3-66.3 months) vs. 21.8 months (range, 1.6-31.6 months); p=0.022). In contrast, VEGF A expression did not correlate with survival. There was a trend toward a higher VEGF A expression in highly vascularized tumors (p=0.08), but failed to reach statistic significance.

Conclusions: The present study indicates, that vascularisation has an important impact on survival of extrahepatic cholangiocarcinoma patients. Other molecules than VEGF A are probably involved in neovascularization in extrahepatic cholangiocarcinoma.