HGF/C-MET system pathways in benign and malignant histotypes of thyroid nodules:: an immunohistochemical characterization
- Autores: Rosaria Maddalena Ruggeri, Enrica Vitarelli, G. Barresi, F. Trimarchi, S. Benvenga, Maria Trovato
- Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 27, Nº. 1, 2012, págs. 113-121
- Idioma: inglés
- Enlaces
-
Resumen
Objective. 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.
Design and methods. 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).
Results. 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.
Conclusions. Our data may have practical implications for the targeted medical therapy of thyroid cancer arising from the follicular epithelium.
