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

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.