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

RET gene rearrangements (RET/PTC1 and RET/PTC3) in papillary thyroid carcinomas from an iodine-rich country (Japan)
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DOI:
10.1002/cncr.21270
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发表时间:
2005-09-01
期刊:
影响因子:
6.2
通讯作者:
Katoh, R
Katoh, R
中科院分区:
医学1区
文献类型:
--
作者:
Nakazawa, T;Kondo, T;Katoh, R

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背景甲状腺乳头状癌中RET重排(RET/PTC)的频率因地理区域而异,据报道,白俄罗斯地区的发病率最高,该地区缺碘,在切尔诺贝利反应堆事故后受到严重污染,而在富碘,未受辐射的日本发病率最低。作者调查了大量日本患者甲状腺肿瘤中RET/PTC的患病率。通过逆转录-聚合酶链反应分析,对215例日本患者的新鲜和石蜡包埋的肿瘤组织进行RET重排(RET/PTC 1和RET/PTC 3)检查,引物位于嵌合区域的侧翼,然后进行直接序列分析。RET/PTC仅见于乳头状癌,未见于其他组织学类型的甲状腺肿瘤。乳头状癌中RET/PTC的总发生率为28.4%,年轻患者的发生率更高,其中41.9%的年轻患者年龄< 20岁,27.6%的患者年龄20-40岁,24.8%的患者年龄> 40岁。在这3个年龄组的患者中,RET/PTC 1的患病率相似,但RET/PTC 3在< 20岁的患者中最常见。当肿瘤进一步根据组织学亚型分组时,实性/实性滤泡性乳头状癌中RET/PTC 3的患病率高于经典乳头状癌。结果提示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,此类肿瘤的发生率并不低,而且似乎与患者年龄有关。因此,目前的结果提出了关于RET/PTC的频率在地理上不同,在日本特别低的信念的问题。
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.