Expression of thyrotrophin receptor gene in thyroid carcinoma is associated with a good prognosis

OBJECTIVE The clinical course of thyroid carcinoma is very variable. It is well known that thyroid carcinomas of similar histology can behave 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 in 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 TSH receptor and c-myc mRNA levels were detected by Northern blot analysis and quantitated by laser densitometry. PATIENTS Thyroid tissues were obtained from five patients with multinodular goitres, 22 with differentiated and three with anaplastic carcinomas. MEASUREMENTS Total cellular RNA was extracted from thyroid tissue specimens and blotted onto nylon membranes. Northern blot analysis was used to detect TSH receptor and c-myc mRNA. The mRNA levels were then quantitated by laser densitometry and compared with each disease stage. RESULTS TSH receptor mRNA levels were significantly lower in carcinomas as compared to benign tumours. With advancing disease stage, the neoplastic tissues generally showed a progressive decline in TSH receptor mRNA levels. Interestingly, in two specimens from patients with distant metastases, TSH receptor mRNA levels were not significantly reduced and were comparable to those in benign tumours. Both patients are still alive, one of them 18 years after operation, indicating that tumour histology is dissociated from its biological behaviour, c-myc mRNA levels were increased but not significantly so in stage 1–3 carcinomas. However, in stage 4 carcinomas c-myc expression was significantly increased. Thus c-myc overex-pression is associated with poor prognosis. Although there is a negative correlation between TSH receptor and c-myc mRNA levels, the correlation was not significant. CONCLUSIONS These results indicate that decreased TSH receptor and increased c-myc gene expression levels are associated with thyroid cell de-differentiation. They are useful markers for thyroid tumour de-differentiation and disease prognosis.