Molecular pathological study for genetic alterations in juvenile thyroid cancer from Japanese patients

背景甲状腺乳头状癌中RET重排（RET/PTC）的频率根据地理区域而显著不同，在切尔诺贝利反应堆事故后碘缺乏和高度污染的白俄罗斯地区报告的发病率最高，在富碘和非辐照国家日本最低。我们调查了大量日本患者甲状腺肿瘤中RET/PTC的患病率。通过RT-PCR和嵌合区侧翼引物对215例日本患者的新鲜石蜡包埋肿瘤组织进行RET重排（RET/PTC 1和RET/PTC 3）检查，然后进行直接序列分析。RET/PTC仅见于乳头状癌（PC），未见于其他组织学类型的甲状腺肿瘤。PC中RET/PTC的总体频率为28.4%，年轻患者的频率更高：20岁以下的年轻患者为41.9%，20至40岁的患者为27.6%，40岁以上的患者为24.8%。在这三个年龄组中，RET/PTC 1的患病率相似，但RET/PTC 3在小于20岁的患者中最常见。当进一步按组织学亚型分组时，实性/实性滤泡PC中RET/PTC 3的患病率高于经典PC。RET/PTC可作为甲状腺乳头状癌的特异性分子标志物。此外，在日本患者中，其在该肿瘤中的发生率并不低，并且似乎与患者年龄相关。因此，我们的研究结果提出了关于RET/PTC的频率在地理上不同，特别是在日本低的教条的问题。

BACKGROUND. The frequency of RET rearrangements (RET/PTC) in papillary thyroid carcinomas varies significantly according to the geographic area, with the highest incidence reported in the Belarus region which is iodine-deficient and highly contaminated after the Chernobyl reactor accident, the lowest in iodine-rich and non-irradiated country, Japan. We 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 RT-PCR with primers flanking the chimeric region, followed by direct-sequence analysis.RESULTS. RET/PTC was only found in papillary carcinomas (PC) and was not observed in other histological types of thyroid tumors. The overall frequency of RET/PTC in PCs was 28.4% with a higher frequency in younger patients : 41.9% in younger patients less than 20 years of age, 27.6% in patients 20 to 40 years of age, and 24.8% in patients over 40 years old. Of these three age groups, the prevalence rate of RET/PTC1 was similar, but RET/PTC3 was most frequently observed in the patients less than 20 years of age. When further grouped by histological subtypes, the prevalence of RET/PTC3 was higher in solid/solid-follicular PCs than in classical PCs.CONCLUSIONS. RET/PTC can be a specific molecular marker for papillary thyroid carcinomas. Furthermore, its incidence in this tumor is not low in Japanese patients, and it seems to be associated with patient age. Therefore, our results raise questions regarding the dogma that frequency of RET/PTC is geographically different and especially low in Japan.