title: Vascular endothelial growth factor-C expression in human gallbladder cancer and its relationship to lymph node metastasis.
abstract: Lymph node metastasis is a major prognostic factor in human cancer. Vascular endothelial growth factor C (VEGF-C) is a lymphangiogenic polypeptide that has been implicated in several human solid tumors. However, the clinical significance of VEGF-C has remained unknown in gallbladder carcinoma. Paraffin-embedded tumor specimens of 52 surgically resected gallbladder cancers were immunohistochemically stained for VEGF-C, VEGF, and CD34. The correlations among VEGF-C expression, VEGF expression, microvessel density (MVD), clinicopathologic features, and clinical outcomes were statistically analyzed. Thirty-three (63%) of the 52 gallbladder cancers were highly positive for VEGF-C protein by immunohistochemistry. VEGF-C expression was significantly correlated with lymphatic vessel involvement, lymph node metastasis, and worse outcomes after operation (p<0.001, p<0.001, p<0.001, respectively), but not with MVD. By the Cox regression model, lymphatic vessel involvement emerged as an independent prognostic parameter. These results suggest that VEGF-C may play a role in tumor progression via lymphangiogenesis and lymph node metastasis in human gallbladder cancer.
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University School of Medicine, Yamaguchi, Japan. t.nakaji@po.cc.yamaguchi-u.ac.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakashima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kondoh
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kitoh
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Ozawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okita
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Harada
authors.forename: Kei
authors.initials: K
authors.lastname: Shiraishi
authors.forename: Shomei
authors.initials: S
authors.lastname: Ryozawa
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Okita
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D016228:Endothelial Growth Factors / Q000032:analysis / Q000378:metabolism*; D005260:Female; D005706:Gallbladder Neoplasms / Q000401:mortality / Q000473:pathology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D008207:Lymphatic Metastasis / Q000473:pathology*; D008222:Lymphokines / Q000032:analysis; D008297:Male; D009367:Neoplasm Staging; D016019:Survival Analysis; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D042442:Vascular Endothelial Growth Factors
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D042442:Vascular Endothelial Growth Factors