High Prevalence of c-RET Expression in Papillary Thyroid Carcinomas from the Korean Population

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. First, somatic rearrangements of RET with variable activation genes are frequently found in papillary thyroid carcinomas. Second, germ-line point mutations are responsible for the development of medullary thyroid carcinomas and multiple endocrine neoplasia type 2 (MEN 2). There are several conflicting reports on the influences of RET expression and RET/PTC rearrangements on the clinical outcome of thyroid cancers. Therefore, the wild-type RET gene expression and RET/PTC-1, RET/PTC-2, RET/PTC-3 rearrangements were examined in thyroid carcinomas and other thyroid diseases. Materials and Methods: Thirty-six papillary thyroid carcinomas (PTCs), 8 follicular thyroid carcinomas (FTCs), 4 anaplastic thyroid carcinomas (ATC), 7 follicular adenomas (FAs), 23 hyperplasias, 6 normal thyroid tissues, and 39 normal portions from each tumor were included in this study. Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical analyses were used to identify the RET gene and RET/PTC rearrangements. Results: From the RT-PCR analysis, 68.9% of the PTCs, a single case of FTC, and 22.2% of the hyperplasias expressed the RET gene. No RET gene expression was observed in ATCs, FAs, or normal thyroid tissues. One RET/PTC-1 and one RET/PTC-2 rearrangement were detected in the PTCs. No RET/PTC-3 rearrangement was detected in any specimen. The immunohistochemical results revealed that 66.7% of PTCs, 28.6% of FAs, and 18.2% of hyperplastic thyroid tissue specimens showed high levels of RET protein expression. Neither the normal thyroid tissues nor the FTCs and ATC, showed high levels of RET protein expression. The two methods are agreed in PTC and hyperplastic nodules, but not in FA and FTC. Conclusion: PTCs among Koreans rarely showed RET/PTC rearrangements, but commonly showed increased RET gene expression. Compared to earlier reports indicating that the expression of the RET gene was limited to PTCs, the RET gene was also expressed in hyperplasias in this study.