Epidermal growth factor receptor and thyrotropin response in human thyroid tissues

Abstract

The content of epidermal-growth-factor receptor (EGFr) and its relation to TSH-response were examined in 27 malignant thyroid tumors (5 follicular, 6 papillary, 5 medullary, 11 anaplastic carcinomas) and in 30 tumor-like lesions (21 hyperplastic goiters and 9 toxic adenomatous goiters). Normal 12 thyroid tissues adjacent to benign tumors with no evidence of macroscopic or microscopic abnormalities were used as control. All thyroid plasma membranes tested showed specific EGF binding. In membranes from toxic adenomas (2.18 +/- 0.73 fmoles/mg protein) and papillary carcinomas (2.80 +/- 0.80) the EGF binding was similar to that of normal thyroid membranes (2.32 +/- 0.73). Hyperplastic goiters showed an EGF binding (4.4 +/- 0.82) slightly higher than normal tissue. The highest and the lowest EGF binding values were found in anaplastic (11.8 +/- 2.78) and medullary (0.50 +/- 0.39) carcinomas, respectively. An inverse correlation between EGFr content and TSH-response was found when anaplastic thyroid tumors were compared to tumor-like lesions. However no correlation was observed in medullary carcinomas which also failed to respond to TSH and in papillary carcinomas which partially respond to thyrotropin.

Efficacy of epidermal growth factor receptor-targeted molecular therapy in anaplastic thyroid cancer cell lines

“…immunohistochemistry and EGF receptor assay have also found that EGFR was frequently overexpressed in anaplastic thyroid cancer (Di Carlo et al, 1990;Westermark et al, 1996). Moreover, in those patients whose thyroid tumours bound more EGF, the prognosis was reported to be poor (Duh et al, 1985).…”

Towards Understanding the Molecular Basis of Thyroid Cancer

“…112 EGF receptor was also detected by radioligand assays in normal, hyperplastic thyroid tissue, as well as benign and malignant tumors. 114 In that study, the level of EGF receptor was found to be greatest in anaplastic tumor tissue. 114 The predominance of EGF receptor expression in papillary carcinoma was extended to the transcripts of c-erbB1 and c-erbB2/neu oncogenes which encode EGF receptor or analogue respectively.…”

“…114 In that study, the level of EGF receptor was found to be greatest in anaplastic tumor tissue. 114 The predominance of EGF receptor expression in papillary carcinoma was extended to the transcripts of c-erbB1 and c-erbB2/neu oncogenes which encode EGF receptor or analogue respectively. 115,116 Aasland et al 116 reported a two-to threefold increase in c-erbB1 and c-erbB2/neu mRNA in papillary carcinomas and their lymph node metastases, as well as in one benign adenoma compared to thyroid tissue.…”

“…Mutations in all three families of ras oncogenes have been detected in both benign and malignant thyroid tumors. 114,132,[137][138][139][140][141][142][143][144][145][146][147][148] Most of the mutations were found at residue 61 of H-ras and N-ras genes. 132,138,146 Variation in the prevalence of ras point mutation thyroid tumors does occur among different series.…”

“…132 An increased frequency of ras mutation in metastatic tumors was observed in some series 146 but not in others. 114,132,146 The ras mutations reported are generally of the transition type (in which a purine is substituted for a purine or a pyrimidine for a pyrimidine), although it has been suggested that transversion mutation (in which a purine is substituted for a pyrimidine and vice versa) may be relevant to dedifferentiated thyroid tumors. 146 Preferential mutation at H-and N-ras 60 is apparently lost in anaplastic carcinoma.…”