RET/PTC Translocations and Clinico-Pathological Features in Human Papillary Thyroid Carcinoma.
RET/PTC Translocations and Clinico-Pathological Features in Human Papillary Thyroid Carcinoma.
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DOI：
10.3389/fendo.2012.00054
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发表时间：
2012
影响因子：
5.2
通讯作者：
Elisei R
中科院分区：
文献类型：
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作者：
Romei C;Elisei R
甲状腺癌是最常见的内分泌肿瘤，约占甲状腺结节的5-10%。乳头状组织型（PTC）是最常见的形式，占所有甲状腺癌的80%。尽管对其流行病学、发病机制、临床和生物学行为了解甚多，但唯一记录在案的PTC危险因素是电离辐射暴露。在PTC中发现了转染期间重排（RET）原癌基因的重排，并已被证明起致病作用。第一个RET重排，命名为RET/PTC，是在1987年发现的。这种重排构成性地激活了滤泡细胞RET酪氨酸激酶结构域的转录，从而触发了MAPK通路的信号传导和不受控制的增殖。到目前为止，已经报道了13种不同类型的RET/PTC重排，但最常见的两种是RET/PTC1和RET/PTC3。电离辐射导致RET/PTC重排，这一点得到了体外研究的支持，并有证据表明RET/PTC，特别是RET/ pc3，在辐射诱导的PTC中非常普遍。然而，许多没有任何辐射暴露史的甲状腺肿瘤也存在类似的RET重排。RET/PTC重排的总体患病率从20%到70%不等，儿童甲状腺癌比成年甲状腺癌更常见。关于RET/PTC重排与PTC预后的关系，有争议的数据报道。RET/PTC3通常与更具侵袭性的表型相关，特别是与更大的肿瘤大小、实变和更晚期的诊断相关，这些都是不良预后因素。相比之下，RET/PTC1重排与PTC的任何临床病理特征无关。RET蛋白和mRNA表达水平与PTC患者预后无相关性，RET/PTC重排与甲状腺分化基因表达水平无相关性。最近，RET/PTC重排的诊断作用被提出。特别是在细胞学不确定的情况下，可以从细胞学样品提取的mRNA中寻找。然而，它可以出现在不可忽略的良性病例百分比的事实和从细胞学材料中提取mRNA的技术挑战使得该程序不适用于常规水平，至少目前如此。
Thyroid carcinoma is the most frequent endocrine cancer accounting for 5–10% of thyroid nodules. Papillary histotype (PTC) is the most prevalent form accounting for 80% of all thyroid carcinoma. Although much is known about its epidemiology, pathogenesis, clinical, and biological behavior, the only documented risk factor for PTC is the ionizing radiation exposure. Rearrangements of the Rearranged during Transfection (RET) proto-oncogene are found in PTC and have been shown to play a pathogenic role. The first RET rearrangement, named RET/PTC, was discovered in 1987. This rearrangement constitutively activates the transcription of the RET tyrosine-kinase domain in follicular cell, thus triggering the signaling along the MAPK pathway and an uncontrolled proliferation. Up to now, 13 different types of RET/PTC rearrangements have been reported but the two most common are RET/PTC1 and RET/PTC3. Ionizing radiations are responsible for the generation of RET/PTC rearrangements, as supported by in vitro studies and by the evidence that RET/PTC, and particularly RET/PTC3, are highly prevalent in radiation induced PTC. However, many thyroid tumors without any history of radiation exposure harbor similar RET rearrangements. The overall prevalence of RET/PTC rearrangements varies from 20 to 70% of PTCs and they are more frequent in childhood than in adulthood thyroid cancer. Controversial data have been reported on the relationship between RET/PTC rearrangements and the PTC prognosis. RET/PTC3 is usually associated with a more aggressive phenotype and in particular with a greater tumor size, the solid variant, and a more advanced stage at diagnosis which are all poor prognostic factors. In contrast, RET/PTC1 rearrangement does not correlate with any clinical–pathological characteristics of PTC. Moreover, the RET protein and mRNA expression level did not show any correlation with the outcome of patients with PTC and no correlation between RET/PTC rearrangements and the expression level of the thyroid differentiation genes was observed. Recently, a diagnostic role of RET/PTC rearrangements has been proposed. It can be searched for in the mRNA extracted from cytological sample especially in case with indeterminate cytology. However, both the fact that it can be present in a not negligible percentage of benign cases and the technical challenge in extracting mRNA from cytological material makes this procedure not applicable at routine level, at least for the moment.