The clinicopathologic significance of the expression of vascular endothelial growth factor-C in intrahepatic cholangiocarcinoma

Objectives: Vascular endothelial growth factor-C (VEGF-C) is known to be an important lymphangiogenetic factor. Lymphatic spread is a key prognostic factor in intrahepatic cholangiocarcinoma (ICC). We studied the expression of VEGF-C in ICC tissues to clarify its clinicopathologic significance. Methods: The expression of VEGF-C in surgical specimens obtained from 36 patients with ICC who underwent hepatic resection was examined by immunohistochemistry and Western blotting. Strong staining was defined as the presence of VEGF-C immunoreactivity in at least 50% of the tumor cells. Immunoreactivity in similar to 10% to similar to 50% of the tumor cells was considered as weak staining, and less than 10% as no staining. Results: Of the 36 patients with ICC, 15 patients (41.7%) showed a strong positive result for VEGF-C. Eleven cases (30.6%) were negative and 10 cases (27.8%) showed weak immunoreactivity. VEGF-C expression was significantly correlated with lymph node metastasis (P = 0.032) and positive surgical margin (P = 0.03). Patients who had strong positive staining for VEGF-C showed significantly less favorable survival rates compared with patients who had negative or weak staining (P < 0.01). Other significant prognostic factors by univariate analysis were vascular invasion, lymph node involvement, and positive surgical margin. Multivariate analysis demonstrated that strong VEGF-C expression (P = 0.028) and vascular invasion (P = 0.021) were independent factors indicating poor prognosis. Conclusions: Our data suggest that VEGF-C expression serves as an independent and important prognostic factor in ICC patients, and it may play an important role in the lymph node metastasis of ICC.