HGF/C-MET system pathways in benign and malignant histotypes of thyroid nodules: an immunohistochemical...

Area of Science:

• Oncology
• Molecular Biology
• Endocrinology

Background:

• The HGF/c-met pathway, involving STAT3, PI3K/Akt, and Rho, drives cell growth and is frequently found in papillary thyroid carcinomas (PTC).
• Understanding the expression patterns of these proteins in various thyroid nodules is crucial for diagnosing and treating thyroid cancer.

Purpose of the Study:

• To investigate the simultaneous expression of HGF, c-met, STAT3, phosphorylated-STAT3, PI3K, Akt, and Rho in a spectrum of thyroid nodules.
• To determine the correlation between the expression of these proteins and the clinical behavior of different thyroid cancer histotypes.

Main Methods:

• Immunohistochemistry was employed to analyze protein expression in 30 colloid nodules, 18 hyperplastic nodules, 20 follicular adenomas, 15 oncocytic adenomas, 20 PTC, 16 follicular carcinomas (FTC), and 6 anaplastic carcinomas (ATC).

Main Results:

• While all 7 proteins were expressed in a subset of follicular adenomas and PTC, the combination HGF/c-met/STAT3/pSTAT3/PI3K was found in all PTC.
• Follicular carcinomas (FTC) and anaplastic carcinomas (ATC) showed high immunoreactivity for PI3K, with epithelial PI3K expression correlating significantly with clinical stage in FTC (r=0.95; p<0.001).
• Epithelial PI3K expression was more prevalent in FTC and ATC compared to PTC.

Conclusions:

• The expression patterns of HGF, c-met, STAT3, PI3K, Akt, and Rho vary across thyroid nodule types.
• Epithelial PI3K expression serves as a potential biomarker for advanced disease in follicular thyroid cancer.
• These findings hold promise for developing targeted medical therapies for thyroid cancers originating from follicular epithelium.