title: The clinicopathologic significance of the expression of vascular endothelial growth factor-C in intrahepatic cholangiocarcinoma.
abstract: OBJECTIVE
  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 approximately 10% to approximately 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.
authors.affiliation: Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Byung Kyu
authors.initials: BK
authors.lastname: Park
authors.forename: Yong-Han
authors.initials: YH
authors.lastname: Paik
authors.forename: Jeong Youp
authors.initials: JY
authors.lastname: Park
authors.forename: Kyung Hwa
authors.initials: KH
authors.lastname: Park
authors.forename: Seungmin
authors.initials: S
authors.lastname: Bang
authors.forename: Seung Woo
authors.initials: SW
authors.lastname: Park
authors.forename: Jae Bock
authors.initials: JB
authors.lastname: Chung
authors.forename: Young Nyun
authors.initials: YN
authors.lastname: Park
authors.forename: Si Young
authors.initials: SY
authors.lastname: Song
mesh_terms: D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016019:Survival Analysis; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C