Heterogeneous distribution of thyrotrophin receptor messenger ribonucleic acid (TSH-R mRNA) in papillary thyroid carcinomas detected by in situ hybridization

Abstract

Objective: TSH suppression therapy has been reported to be effective in some cases of papillary carcinoma of the thyroid. However, there has been little information regarding the status of expression of TSH-R mRNA in papillary carcinomas. Therefore, we examined the expression of TSH receptor (TSH-R) mRNA in thyroid tumours by in situ hybridization.

Design: Surgically resected thyroid tumour specimens were used. The expression level of TSH-R mRNA was detected by in situ hybridization, and the difference between tumours and their adjacent normal thyroid tissues was assessed.

Patients: Tumours and adjacent normal thyroid tissues were obtained from nine patients with differentiated papillary carcinomas and eight with adenomas.

Measurements: We performed in situ hybridization on frozen sections of thyroid tissues. Digoxigenin-labelled oligonucleotide was used to hybridize and to detect TSH-R mRNA. We counted positively stained cells and non-stained cells in each section, calculated the positivity of stained cells and assessed the distribution of positively stained cells.

Results: In normal thyroid tissue, the positivity was 95.3 +/- 2.3% (mean +/- SD) and the distribution of TSH-R mRNA was homogeneous. In adenoma, positivity was 93.5 +/- 4.4%. In most cases of adenoma, the distribution was homogeneous. In papillary carcinoma, the expression level of TSH-R mRNA was significantly lower and the positivity was 81.9 +/- 12.6%. Furthermore, in five cases of papillary carcinoma, the distribution was heterogeneous; four of these cases were stage 3, while the remaining case was stage 1. Three of the four cases with a homogeneous distribution were stage 1, while one case was stage 3.

Conclusions: The heterogeneity of TSH-R mRNA distribution suggests the effect of TSH on carcinoma cells may be variable. Furthermore, papillary carcinomas of advanced clinical stage showed a tendency to low expression and heterogeneous distribution of TSH-R mRNA.