title: HGF/C-MET system pathways in benign and malignant histotypes of thyroid nodules: an immunohistochemical characterization.
abstract: Upon binding with HGF, the thyrosine-kinase receptor c-met induces cell growth, scattering and morphogenic effects via the trasducers STAT3 and phosphorylated-STAT3, PI3K/Akt, Rho. HGF, c-met and STAT3 are expressed with very high frequency in papillary thyroid carcinomas (PTC), suggesting a role in PTC. Herein we first investigate the simultaneous expression of HGF, c-met, STAT3, phosphor-STAT3, PI3K, Akt and Rho in thyroid nodules.
  
  
  
  Using immunohistochemistry, we studied: 30 colloid nodules (CN), 18 hyperplastic nodules (HN), 20 follicular adenomas (FA), 15 oncocytic adenomas (OA), 20 PTC, 16 follicular carcinomas (FTC) and 6 anaplastic carcinomas (ATC).
  
  
  
  All 7 proteins were expressed in 15% of FA (with HGF, PI3K and Rho stromal reactivity) and 25% of PTC, and the combination HGF/c-met/STAT3/ pSTAT3/PI3K was expressed by all PTC, each protein being expressed by tumor cells. In contrast, 13/16 FTC (81%) exhibited immunoreactivity for PI3K (both epithelial and stromal), and 100% of ATC was PI3K+ (both epithelial and stromal) and Rho+ (epithelial). Epithelial expression of PI3K correlated with the clinical behavior of histotypes and, within FTC, the proportion of PI3K+ cells correlated with both the clinical and pathological stage (r=0.95; p<0.001). As for the shared epithelial expression of PI3K, this concerned approximately one-fourth of tumor cells in FTC and ATC vs one-thirtieth in PTC.
  
  
  
  Our data may have practical implications for the targeted medical therapy of thyroid cancer arising from the follicular epithelium.
authors: Dipartimento Clinico-Sperimentale di Medicina e Farmacologia, Sezione di Endocrinologia, University of Messina, Messina, Italy.
authors: R M
authors: RM
authors: Ruggeri
authors: E
authors: E
authors: Vitarelli
authors: G
authors: G
authors: Barresi
authors: F
authors: F
authors: Trimarchi
authors: S
authors: S
authors: Benvenga
authors: M
authors: M
authors: Trovato
mesh_terms: D018263:Adenocarcinoma, Follicular; D000236:Adenoma / Q000737:chemistry* / Q000473:pathology; D002277:Carcinoma; D002291:Carcinoma, Papillary; D004847:Epithelial Cells / Q000737:chemistry; D017228:Hepatocyte Growth Factor / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D009367:Neoplasm Staging; D058539:Phosphatidylinositol 3-Kinase / Q000032:analysis; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis*; D050796:STAT3 Transcription Factor / Q000032:analysis; D017154:Stromal Cells / Q000737:chemistry; D000077273:Thyroid Cancer, Papillary; D065646:Thyroid Carcinoma, Anaplastic; D013964:Thyroid Neoplasms / Q000737:chemistry* / Q000473:pathology; D016606:Thyroid Nodule / Q000737:chemistry* / Q000473:pathology; D020741:rho GTP-Binding Proteins / Q000032:analysis
chemical_list: C066855:HGF protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D017228:Hepatocyte Growth Factor; D058539:Phosphatidylinositol 3-Kinase; D019859:Proto-Oncogene Proteins c-met; D051057:Proto-Oncogene Proteins c-akt; D020741:rho GTP-Binding Proteins