259 THYROID Volume 15, Number 3, 2005 © Mary Ann Liebert, Inc. High Prevalence of c-RET Expression in Papillary Thyroid Carcinomas from the Korean Population Sihoon Lee, 1 Soon Won Hong, 2 Woo Chul Moon, 3 Myung Ryurl Oh, 3 Jin Kyung Lee, 3 Chul Woo Ahn, 1 Bong Soo Cha, 1 Kyung Rae Kim, 1 Hyun Chul Lee, 1 and Sung-Kil Lim 1 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 rearrange- ments 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 re- arrangements. 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 re- arrangement 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 expres- sion. 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. Com- pared 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. Introduction T HYROID CANCER is the most common endocrine malig- nancy, with papillary carcinomas the most frequent sub- type. As the understanding of the molecular pathophysiol- ogy of thyroid cancer advances, many genes have been found to be related to the development of thyroid cancer. Activa- tions of the TRK and RET genes, receptors for nerve growth factor and glial cell-derived neurotrophic factor, respec- tively, are found in papillary thyroid carcinomas. Of these two genes, the RET gene, which is located on the long arms of chromosome 10, is normally expressed in tissues origi- nating from the neural crest, but not in normal thyroid fol- licular cells (1) (Fig. 1). The activation of the RET proto-onco- gene contributes to the development of human cancers in two different ways: somatic rearrangements of RET, with a variety of activating genes, are frequently found in papillary thyroid carcinomas, and germ-line mutations with point mu- tations are mainly responsible for the development of in- herited cancer syndrome and multiple endocrine neoplasia type 2 (2). Several forms of the RET/PTC oncogene have been iden- tified, including RET/PTC-1, RET/PTC-2, and RET/PTC-3, and in these forms, the RET proto-oncogene is fused to the H4 gene on chromosome 10q21 (3,4), the regulatory sub- unit RI of the cyclic adenosine monophosphate (cAMP)- dependent protein kinase A gene on 17q23 (5) and the Ele 1 gene on 10q11.2 (6), respectively. A few RET gene re- arrangements, although low in frequency, have also been found. RET/PTC rearrangements have been reported to oc- Departments of 1 Internal Medicine and 2 Pathology, Yonsei University College of Medicine, Seoul, Korea. 3 GoodGene Inc. Seoul, Korea. This abstract was presented at the 85th Annual Meeting of the Endocrine Society, Philadelphia, Pennsylvania.