title: Intratumoral c-Met expression is associated with vascular endothelial growth factor C expression, lymphangiogenesis, and lymph node metastasis in oral squamous cell carcinoma: implications for use as a prognostic marker.
abstract: Hepatocyte growth factor has been identified as a lymphangiogenic factor in experimental animal models. However, the correlation between hepatocyte growth factor or c-Met expression and lymphangiogenesis in human spontaneous tumors has been rarely reported, and the distribution pattern of c-Met on tumor-related lymphatic vessels remains to be further investigated. Lymphatic vessel density, lymphatic invasion, the expression of hepatocyte growth factor, c-Met, and vascular endothelial growth factor C proteins were evaluated by immunohistochemistry in 76 cases of oral squamous cell carcinoma. The distribution of c-Met on lymphatic endothelium was examined. High expression of c-Met in tumor cells was significantly associated with advanced clinical stage (P = .045), high expression of vascular endothelial growth factor-C (P < .001), higher peritumoral lymphatic vessel density (P = .003), higher incidence of peritumoral lymphatic invasion (P = .032), and positive lymph node status (P = .005), in spite of its negative expression on most lymphatic vessels. Patients with high-c-Met expression tumors exhibited shorter overall survival and disease-free survival (P < .001 and P = .010, respectively). Taken together, our results provide indirect evidence for an association and possible regulatory link of c-Met with the lymphangiogenic factor, vascular endothelial growth factor C, and, by extension, with lymphangiogenesis and lymph node metastasis, suggesting important prognostic significance of c-Met for patients with oral squamous cell carcinoma.
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Si-Hua
authors.initials: SH
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Feng
authors.forename: Cheng-Ge
authors.initials: CG
authors.lastname: Hua
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.forename: Xiu-Fa
authors.initials: XF
authors.lastname: Tang
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism; D004729:Endothelium, Lymphatic / Q000378:metabolism; D005260:Female; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000378:metabolism / Q000473:pathology; D008297:Male; D009062:Mouth Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D016019:Survival Analysis; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met