CELL KINETICS, DNA CONTENT AND TSH RECEPTOR‐ADENYLATE CYCLASE SYSTEM IN DIFFERENTIATED THYROID CANCER

Abstract

The purpose of this study was to elucidate the changes of the TSH receptor‐adenylate cyclase system in differentiated thyroid carcinomas, and their relationships with nuclear DNA content, cell kinetics and clinical stage. The results showed that the papillary carcinomas had an impaired TSH receptor‐adenylate cyclase system. The production of cAMP stimulated by TSH was decreased when compared with non‐cancerous tissue and high‐affinity TSH receptors were reduced in number or even completely lost (nine in 24 cases). Follicular carcinomas also showed a reduction in, or even complete loss, of high‐affinity TSH receptor (one in five cases). However, the responses to the stimulation of TSH, Gpp (NH)p and forskoiin were not different from those in non‐cancerous tissue. Papillary and follicular cancer cells showed more proliferative activity than those in non‐cancerous tissue. Follicular carcinomas contained more hyperploid cells (DNA content >2.5 C) than papillary carcinomas. There were no differences in cell kinetics, DNA content or the effects of Gpp (NH)p or forskoiin on adenylate cyclase activity between those papillary carcinomas with high‐affinity TSH receptor and those without. However, the presence of high‐affinity TSH receptors had higher cAMP generation stimulated by TSH. The patients having papillary carcinomas in the absence of high‐affinity TSH receptors were all in clinical stage'III. These studies suggest that TSH receptors are the major sites influenced in the TSH receptor‐adenylate cyclase system in papillary carcinomas. The TSH receptor‐adenylate cyclase system of papillary carcinomas differs more from normal than does that of follicular carcinomas. That follicular carcinomas are usually more aggressive than papillary carcinomas may be partly explained by more hyperploid cells in follicular carcinomas. The absence of high‐affinity TSH receptor in papillary carcinomas may mean a more advanced clinical stage and poorer prognosis.