Nerve growth factor-beta expression is associated with lymph node metastasis and nerve infiltration in human hilar cholangiocarcinoma

Abstract

Background: Angiogenesis and lymphangiogenesis are important processes in the progression of malignant tumors. Previous studies have shown that nerve growth factor-beta (NGF-beta) can promote the initiation and progression of many tumors. In addition, vascular endothelial growth factor-C (VEGF-C) has become recognized as the most important lymphangiogenic factor. In the present study, the expression of NGF-beta in human hilar cholangiocarcinoma and its relationship with lymphangiogenesis, lymph node metastasis, nerve infiltration, and VEGF-C expression was investigated.

Methods: Nerve growth factor-beta and VEGF-C expression were investigated by immunohistochemistry in samples from 28 cases of hilar cholangiocarcinoma. The lymphatic vessel density (LVD) in the tumor tissue that indicated lymphangiogenesis were calculated by immunostaining with the lymphendothelial-specific antibody D2-40. The relationship between NGF-beta expression and VEGF-C expression, lymphangiogenesis, lymph node metastasis, and nerve infiltration was evaluated.

Results: The overexpression of NGF-beta and VEGF-C occurred in 57.1% (16/28) and 46.4% (13/28) of tumor samples, respectively. Nerve growth factor-beta overexpression was highly correlated with VEGF-C overexpression (P = 0.005), LVD (P < 0.001), lymph node metastasis (P = 0.021), nerve infiltration (P = 0.019), and tumor stage (P = 0.040). Furthermore, VEGF-C overexpression was highly correlated with LVD (P < 0.001) and lymph node metastasis (P < 0.001). However, there was no statistic significance in the relation between NGF-beta expression and sex (P = 0.185), age (P = 0.387), maximal tumor size (P = 0.736), Bismuth classification (P = 0.627) as well as histological grade (P = 0.203).

Conclusions: Nerve growth factor-beta might promote lymph node metastasis and nerve infiltration in human hilar cholangiocarcinoma.