EXPRESSION OF THYROTROPIN RECEPTOR GENE IN THYROID-CARCINOMA IS ASSOCIATED WITH A GOOD PROGNOSIS

OBJECTIVE The clinical course of thyroid carcinoma is very variable. I t is well known that thyroid carcinomas of similar histology can behav e differently in terms of local invasion and distant metastases: there is no reliable way to predict the disease course with confidence. In the present study we compared the TSH receptor and c-myc mRNA levels i n different stages of thyroid carcinomas to identify whether they are useful markers for thyroid tumour biological behaviour and prognosis. DESIGN Thyroid tumour specimens were used as the source of RNA. The TS H receptor and c-myc mRNA levels were detected by Northern blot analys is and quantitated by laser densitometry. PATIENTS Thyroid tissues wer e obtained, from five patients with multinodular goitres, 22 with diff erentiated and three with anaplastic carcinomas. MEASUREMENTS Total ce llular RNA was extracted from thyroid tissue specimens and blotted ont o nylon membranes. Northern blot analysis was used to detect TSH recep tor and c-myc mRNA. The mRNA levels were then quantitated by laser den sitometry and compared with each disease stage. RESULTS TSH receptor m RNA levels were significantly lower in carcinomas as compared to benig n tumours. With advancing disease stage, the neoplastic tissues genera lly showed a progressive decline in TSH receptor mRNA levels. Interest ingly, in two specimens from patients with distant metastases, TSH rec eptor mRNA levels were not significantly reduced and were comparable t o those in benign tumours. Both patients are still alive, one of them 18 years after operation, indicating that tumour histology is dissocia ted from its biological behaviour. c-myc mRNA levels were increased bu t not significantly so in stage 1-3 carcinomas. However, in stage 4 ca rcinomas c-myc expression was significantly increased. Thus c-myc over expression is associated with poor prognosis. Although there is a nega tive correlation between TSH receptor and c-myc mRNA levels, the corre lation was not significant. CONCLUSIONS These results indicate that de creased TSH receptor and increased c-myc gene expression levels are as sociated with thyroid cell de-differentiation. They are useful markers for thyroid tumour de-differentiation and disease prognosis.