Thyroid carcinoma after Chernobyl latent period, morphology and aggressiveness
Thyroid carcinoma after Chernobyl latent period, morphology and aggressiveness
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DOI：
10.1038/sj.bjc.6601860
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发表时间：
2004-06-01
影响因子：
8.8
通讯作者：
Thomas, GA
中科院分区：
文献类型：
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作者：
Williams, ED;Abrosimov, A;Thomas, GA
在切尔诺贝利事故后放射性沉降物中暴露于高水平短寿命同位素的人群中发生的大量乳头状甲状腺癌，为将潜伏期与肿瘤生物学联系起来提供了独特的机会。我们发现，与潜伏期较长的肿瘤相比，短潜伏期与结构分化明显较低的表型肿瘤相关，肿瘤周围纤维化明显较少，侵袭性扩散明显更强。相反，分化类型（乳头状或滤泡结构）与暴露年龄有关。这些发现表明，暴露时的初始突变在肿瘤潜伏期和侵袭性中起主要作用。我们和其他人已经证明，在这些短潜伏期肿瘤中，RET-PTC3重排与实体形态有关，而经典乳头状癌更常显示RET-PTC1重排。对转基因小鼠的研究也显示了类似的结果，并且体外研究表明，RET-PTC3诱导的生长速度比RET-PTC1更快。因此，我们认为，在切尔诺贝利后肿瘤的早期调查中发现的固体形态、RET-PTC3重排的高频率和侵袭性行为是短潜伏期的特征，而不是诱变原的性质，并且暴露于切尔诺贝利放射性尘埃的人出现了具有不同潜伏期、不同突变模式和不同临床行为的乳头状癌的连续重叠波。(C) 2004年英国癌症研究所。
The large numbers of papillary thyroid carcinomas that have occurred in those exposed to high levels of short-lived isotopes in fallout after Chernobyl provide a unique opportunity to correlate latency and tumour biology. We show that short latency is associated with tumours with a phenotype that is significantly less structurally differentiated, shows significantly less peritumour fibrosis, and significantly more invasive spread when compared to tumours with a longer latent period. In contrast, the type of differentiation (papillary or follicular architecture) is associated with age at exposure. These findings suggest that the initial mutation at the time of exposure played a major role in tumour latency and aggressiveness. We and others have shown that RET-PTC3 rearrangements are associated with the solid morphology seen in these short latency tumours, while classical papillary carcinomas more often show RET-PTC1 rearrangements. Studies in transgenic mice show similar findings, and in vitro studies show that RET-PTC3 induces more rapid growth than RET-PTC1. We therefore suggest that the solid morphology, high frequency of RET-PTC3 rearrangements and aggressive behaviour noted in early investigations of post-Chernobyl tumours were characteristic of short latency rather than the nature of the mutagen, and that successive overlapping waves of papillary carcinoma with differing latency, differing patterns of mutations and differing clinical behaviour are occurring in those exposed to Chernobyl fallout. (C) 2004 Cancer Research UK.