The Clinicopathological Results of Thyroid Cancer With <i>BRAF</i> <i>V600E</i> Mutation in the Young Population of Fukushima
Manabu Iwadate, Norisato Mitsutake, Michiko Matsuse, Toshihiko Fukushima, Satoshi Suzuki, Satoshi Suzuki, Yoshiko Matsumoto, Chiyo Ookouchi, Hiroshi Mizunuma, Izumi Nakamura, Keiichi Nakano, Atsuhiko Sakamoto, Mitsuyoshi Hirokawa, Masahiro Ito, Hiroshi Naganuma, Yuko Hashimoto, Hiroki Shimura, Shunichi Yamashita, Shinichi Suzuki, Shinichi Suzuki
Abstract
BACKGROUND: Thyroid ultrasound screening for children aged 0 to 18 years was performed in Fukushima following the accident at the Fukushima Daiichi Nuclear Power Plant. As a result, many thyroid cancer cases were detected. To explore the carcinogenic mechanisms of these cancers, we analyzed their clinicopathological and genetic features. METHODS: We analyzed 138 cases (52 males and 86 females) who had undergone surgery between 2013 and 2016 at Fukushima Medical University Hospital. Postoperative pathological diagnosis revealed 136 (98.6%) cases of papillary thyroid cancer (PTC). RESULTS: The BRAFV600E mutation was detected using direct DNA sequencing in 96 (69.6%) of the thyroid cancer cases. In addition, oncogenic rearrangements were detected in 23 cases (16.7%). Regarding chromosomal rearrangements, 8 (5.8%) RET/PTC1, 6 (4.3%) ETV6(ex4)/NTRK3, 2 (1.4%) STRN/ALK, and 1 each of RET/PTC3, AFAP1L2/RET, PPFIBP/RET, KIAA1217/RET, ΔRFP/RET, SQSTM1/NTRK3 and TPR/NTRK1 were detected. Tumor size was smaller in the BRAFV600E mutation cases (12.8 ± 6.8 mm) than in wild-type BRAF cases (20.9 ± 10.5 mm). In the BRAFV600E mutation cases, 83 (86.5%) showed lymph node metastasis, whereas 26 (61.9%) of the wild-type BRAF cases showed lymph node metastasis. CONCLUSIONS: The BRAFV600E mutation was mainly detected in residents of Fukushima, which was different from post-Chernobyl PTC cases with RET/PTC3 rearrangement. PTC with the BRAFV600E mutation was smaller but was shown in the high rate of central cervical lymph node metastasis than the wild-type BRAF PTC in the young population of Fukushima.