title: Upregulation of HGF and c-MET is associated with subclinical central lymph node metastasis in papillary thyroid microcarcinoma.
abstract: BACKGROUND
  Identification of a novel biomarker of subclinical lymph node metastasis (SLNM) in papillary thyroid microcarcinoma (PTMC) could provide important clues regarding SLNM in PTMC. We evaluated the significance of HGF and c-Met expression in surgically removed tumor tissue from PTMC patients as a predictive marker of SLNM.
  
  
  METHODS
  We analyzed the immunohistochemical relationship between HGF and c-Met expression and SLNM in 113 surgically treated PTMC patients with clinically negative nodes presurgery. In addition, we explored whether HGF/c-Met pathway activation enhanced the in vitro migration and invasion of PTC cells.
  
  
  RESULTS
  Positive immunohistochemical HGF and c-Met staining was found in 107 (95 %) and 103 (91 %) cases, respectively. The HGF staining distribution was as follows: no staining in 6 cases, weak staining in 43, moderate staining in 55, and strong staining in 9. Of the nine cases with strong HGF staining, eight (89 %) had SLNM. The c-Met staining distribution was as follows: no staining in 10 cases, weak staining in 39, moderate staining in 59, and strong staining in 5. Of the five cases with strong c-Met staining, three (60 %) had SLNM. The presence of SLNM was strongly correlated with HGF and c-Met expression in PTMC in a univariate analysis (P < 0.05). HGF overexpression was also associated with SLNM in a multivariate analysis (P < 0.05). Stimulation with exogenous HGF and constitutive activation of c-Met enhanced the migration and invasion of PTC cells in vitro by enhancing VEGF-A expression.
  
  
  CONCLUSIONS
  HGF/c-Met pathway activation is associated with SLNM of the central neck in PTMC.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Cancer Research Institute, Chungnam National University College of Medicine, Daejeon, The Republic of Korea.
authors.forename: Bon Seok
authors.initials: BS
authors.lastname: Koo
authors.forename: Jin Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Sung Tae
authors.initials: ST
authors.lastname: Seo
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Yoon
authors.forename: Ki Ryun
authors.initials: KR
authors.lastname: Kwon
authors.forename: Sung Ha
authors.initials: SH
authors.lastname: Kim
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Kwon
authors.forename: Won Jin
authors.initials: WJ
authors.lastname: Bae
authors.forename: Young Chang
authors.initials: YC
authors.lastname: Lim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002291:Carcinoma, Papillary / Q000378:metabolism* / Q000556:secondary*; D005260:Female; D005500:Follow-Up Studies; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000556:secondary*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met