title: 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.
authors.affiliation: Department of General Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, Guangdong Province, China.
authors.forename: Lei-Bo
authors.initials: LB
authors.lastname: Xu
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.forename: Guo-Quan
authors.initials: GQ
authors.lastname: Gao
authors.forename: Xian-Huan
authors.initials: XH
authors.lastname: Yu
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000378:metabolism / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic; D018281:Cholangiocarcinoma / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D020932:Nerve Growth Factor / Q000096:biosynthesis*; D010524:Peripheral Nervous System Neoplasms / Q000378:metabolism / Q000473:pathology*; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis
chemical_list: D042582:Vascular Endothelial Growth Factor C; D020932:Nerve Growth Factor