Demonstration of a TGF‐α‐EGF‐receptor autocrine loop and c‐myc protein over‐expression in papillary thyroid carcinomas

Abstract

Autocrine growth stimulation has been identified in several types of human cancer. In the present study we wanted to establish whether autocrine stimulation of the epidermal-growth-factor receptor (EGF-r) by its ligand, transforming growth factor alpha (TGF-α) occurs in thyroid neoplasia. We examined 190 fresh, frozen thyroid tissue samples from 70 patients by immunohistochemistry with antibodies to EGF-r, TGF-α, c-erbB-2 and c-myc. EGF-r expression was detected in 17 out of 19 papillary carcinomas, TGF-a expression in 10, and c-erbB-2 expression in IS. No papillary carcinoma expressed TGF-a without also expressing EGF-r. Concomitant expression of EGF-r, TGF-α and c-erbB-2 was seen in 7 papillary carcinomas. No EGF-r, TGF-α or c-erbB-2 immunopositivity was found in normal-appearing thyroid tissue (25 cases), whereas a few of the non-neoplastic lesions (colloid goitres and diffuse hyperplasias) expressed either EGF-r or TGF-α. c-myc expression was detectable in all tissue samples, and expression was invariably nuclear. Increased expression was observed in 10 out of 19 papillary carcinomas, and 8 of these also co-expressed EGF-r and TGF-α. In situ hybridization confirmed the presence of TGF-α mRNA in tumour epithelium of TGF-α-immunopositive samples. The concomitant expression of EGF-r, TGF-α and TGF-α mRNA gives evidence for a TGF-α-EGF-r autocrine loop in thyroid papillary carcinomas. The increased c-myc expression may reflect the proliferative advantage of these tumours.