한국인의 갑상선질환에서 RET 유전자 발현

Abstract

Background: Activation of the RET proto-oncogene, located on the long arms of chromosome 10, contributes to the development of thyroid cancers in two different ways. Somatic rearrangements of RET with variable genes of activation are frequently found in papillary thyroid carcinomas. And Ggerm-line point mutations are responsible for the development of medullary thyroid carcinoma and the multiple endocrine neoplasia type 2(MEN2). There are several conflicting reports on the influences of RET expression and RET/PTC rearrangements on the clinical outcome of thyroid cancer. Therefore, we performed an examination of RET expression and RET/PTC-1, -2, -3 rearrangements in papillary thyroid carcinomas and other thyroid diseases.

Methods: Twenty-six papillary thyroid carcinomas(PTCs), three follicular thyroid carcinomas (FTCs), one anaplastic thyroid carcinoma(ATC), five follicular adenomas(FAs), nineteen hyperplasias, and two normal thyroid tissues were included in this study. RT-PCR and immunohistochemistry analysis were done to identify RET gene, RET/PTC rearrangements, and ret RET protein expression.

Results: By RT-PCR, 89.4% of PTCs, 100% of FTCs, and 62.1% of hyperplasias expressed the RET gene, but no RET was observed in ATCs, FAs, and normal thyroid tissues. RET/PTC-1, -2,-3 rearrangements were not detected in any specimens. Immunohistochemical results revealed that 76.9% of PTCs, 50% of FAs, 52.3% of hyperplasias, and 20.6% of normal thyroid tissues expressed the RET ret protein, but FTCs and ATCs did not. Most PTCs showed strong cytoplasmic positivity in RET ret immunostaining, but the positive non- PTCs expressed weak and membranous staining. Overall, the two methods for detecting RET gene, RT-PCR and immunohistochemistry showed similar results.

Conclusion: The RET gene was highly expressed in PTCs. In contrast to the previous reports of that theRET gene expression of RET gene is being limited to PTCs, RET was also expressed in hyperplasias, Fas, and normal thyroid tissues. However, the pattern and the degree of expression of the RET ret protein in non- PTCs were are different from those in PTCs.