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

Int J Cancer. 1993 Aug 19;55(1):37-43. doi: 10.1002/ijc.2910550108.


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-alpha) occurs in thyroid neoplasia. We examined 190 fresh, frozen thyroid tissue samples from 70 patients by immunohistochemistry with antibodies to EGF-r, TGF-alpha, c-erbB-2 and c-myc. EGF-r expression was detected in 17 out of 19 papillary carcinomas, TGF-alpha expression in 10, and c-erbB-2 expression in 15. No papillary carcinoma expressed TGF-alpha without also expressing EGF-r. Concomitant expression of EGF-r, TGF-alpha and c-erbB-2 was seen in 7 papillary carcinomas. No EGF-r, TGF-alpha 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-alpha. 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-alpha. In situ hybridization confirmed the presence of TGF-alpha mRNA in tumour epithelium of TGF-alpha-immunopositive samples. The concomitant expression of EGF-r, TGF-alpha and TGF-alpha mRNA gives evidence for a TGF-alpha-EGF-r autocrine loop in thyroid papillary carcinomas. The increased c-myc expression may reflect the proliferative advantage of these tumours.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Papillary / metabolism*
  • ErbB Receptors / biosynthesis*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins c-myc / biosynthesis*
  • RNA, Messenger / analysis
  • RNA, Neoplasm / analysis
  • Receptor, ErbB-2
  • Thyroid Neoplasms / metabolism*
  • Transforming Growth Factor alpha / biosynthesis*
  • Transforming Growth Factor alpha / physiology


  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • RNA, Neoplasm
  • Transforming Growth Factor alpha
  • ErbB Receptors
  • Receptor, ErbB-2