RET gene rearrangements (RET/PTC1 and RET/PTC3) in papillary thyroid carcinomas from an iodine‐rich country (Japan)

• Published in: Cancer Vol. 104; no. 5; pp. 943 - 951
• Main Authors: Nakazawa, Tadao, Kondo, Tetsuo, Kobayashi, Yoshihiko, Takamura, Noboru, Murata, Shin‐ichi, Kameyama, Kaori, Muramatsu, Akira, Ito, Kohichi, Kobayashi, Makio, Katoh, Ryohei
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.09.2005; Wiley-Liss
• Subjects: Adult; Aged; Biological and medical sciences; Carcinoma, Papillary - genetics; Carcinoma, Papillary - pathology; Endocrinopathies; Female; Gene Rearrangement; Humans; Japanese; Male; Malignant tumors; Medical sciences; Middle Aged; Oncogene Proteins, Fusion - genetics; papillary thyroid carcinoma; patient age; Protein-Tyrosine Kinases - genetics; RET rearrangement; reverse transcriptase‐polymerase chain reaction; Thyroid Neoplasms - genetics; Thyroid Neoplasms - pathology; Thyroid. Thyroid axis (diseases); Tumors; Asia; Japan; Endocrinopathy; Human; Papillary carcinoma; RET rearrangement; Countries; Thyroid diseases; Malignant tumor; Japanese; Thyroid carcinoma; reverse transcriptase-polymerase chain reaction; Thyroid cancer; Cancerology; C-Onc gene; Gene rearrangement; patient age; Molecular biology; papillary thyroid carcinoma; Reverse transcription polymerase chain reaction; Age; Protooncogene; Iodine
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.21270

BACKGROUND The frequency of RET rearrangements (RET/PTC) in papillary thyroid carcinomas varies significantly according to geographic area, with the greatest incidence reported in the Belarus region, which is iodine‐deficient and was contaminated severely after the Chernobyl reactor accident, and with the lowest incidence in iodine‐rich, nonirradiated Japan. The authors investigated the prevalence of RET/PTC in a large number of thyroid tumors from Japanese patients. METHODS Fresh and paraffin embedded tumor tissues from 215 Japanese patients were examined for RET rearrangements (RET/PTC1 and RET/PTC3) by means of reverse transcriptase‐polymerase chain reaction analysis, with primers flanking the chimeric region, followed by direct‐sequence analysis. RESULTS RET/PTC was found only in papillary carcinomas and was not observed in other histologic types of thyroid tumors. The overall frequency of RET/PTC in papillary carcinomas was 28.4%, with a greater frequency in younger patients, including 41.9% of younger patients age < 20 years, 27.6% of patients age 20–40 years, and 24.8% of patients age > 40 years. Among the patients in these 3 age groups, the prevalence rate of RET/PTC1 was similar, but RET/PTC3 was observed most frequently among patients age < 20 years. When the tumors were grouped further according to histologic subtypes, the prevalence of RET/PTC3 was greater in solid/solid‐follicular papillary carcinomas than in classic papillary carcinomas. CONCLUSIONS The results indicated that RET/PTC may be useful as a specific molecular marker for papillary thyroid carcinomas. Furthermore, its incidence in such tumors was not low in Japanese patients, and it seemed to be associated with patient age. Therefore, the current results raise questions regarding the belief that the frequency of RET/PTC differs geographically and is especially low in Japan. Cancer 2005. © 2005 American Cancer Society. The overall frequency of RET gene rearrangements (RET/PTC1 and RET/PTC3) in papillary carcinoma tissues was 28.4%, and such rearrangements occurred with greater frequency in younger patients, including 41.9% of younger patients age < 20 years, 27.6% of patients age 20–40 years, and 24.5% of patients age > 40 years. The current results raise questions regarding the belief that the frequency of RET/PTC differs geographically and is especially low in iodine‐rich countries.