Learoyd D L, Messina M, Zedenius J, Guinea A I, Delbridge L W, Robinson B G
Kolling Institute of Medical Research, Department of Endocrinology, Royal North Shore Hospital and University of Sydney, Australia.
J Clin Endocrinol Metab. 1998 Oct;83(10):3631-5. doi: 10.1210/jcem.83.10.5152.
The prevalence of RET/PTC rearrangements in papillary thyroid carcinomas (PTCs) varies widely in different studies, and an association of RET/PTC presence with tumor behavior remains to be clarified. A prospective study of 50 adult PTCs examined, using RT-PCR, the prevalence of the 3 main RET rearrangements and also of RET tyrosine kinase (TK) domain sequence expression. The genetic findings were correlated with the MACIS clinical prognostic score and with individual clinical parameters. Three of the patients had been exposed to radiation in childhood or adolescence. Four of the PTCs contained RET/PTC1, confirmed by sequencing, and none contained RET/PTC2 or RET/PTC3. The prevalence of RET rearrangements overall was 8%, but in the subgroup of 3 radiation-exposed patients it was 66.6%. Interestingly, RET tyrosine kinase domain messenger ribonucleic acid was detectable in 70% of PTCs using RET exon 12/13 primers and was detectable in 24% of PTCs using RET exon 15/17 primers. RT-PCR for calcitonin and RET extracellular domain, however, was negative. There was no association between the presence or absence of RET/PTC in the patient's tumor and clinical parameters. We conclude that RET/PTC1 is the predominant rearrangement in PTCs from adults with a history of external irradiation in childhood. RET TK messenger ribonucleic acid expression is common in PTCs, using RT-PCR, and cannot be used to infer the presence of specific RET rearrangements or of RET activation.
在不同研究中，甲状腺乳头状癌（PTC）中RET/PTC重排的发生率差异很大，RET/PTC的存在与肿瘤行为之间的关联仍有待阐明。一项对50例成年PTC患者的前瞻性研究，使用逆转录聚合酶链反应（RT-PCR）检测了3种主要RET重排的发生率以及RET酪氨酸激酶（TK）结构域序列的表达。将基因检测结果与MACIS临床预后评分及个体临床参数进行关联分析。其中3例患者在儿童期或青春期接受过辐射。4例PTC经测序证实含有RET/PTC1，无一例含有RET/PTC2或RET/PTC3。总体RET重排发生率为8%，但在3例有辐射暴露史的患者亚组中，发生率为66.6%。有趣的是，使用RET外显子12/13引物，70%的PTC中可检测到RET酪氨酸激酶结构域信使核糖核酸，使用RET外显子15/17引物，24%的PTC中可检测到该信使核糖核酸。然而，降钙素和RET细胞外结构域的RT-PCR检测结果为阴性。患者肿瘤中RET/PTC的有无与临床参数之间无关联。我们得出结论，RET/PTC1是有儿童期外照射史的成年PTC患者中的主要重排类型。使用RT-PCR检测，RET TK信使核糖核酸表达在PTC中很常见，但不能用于推断特定RET重排或RET激活的存在。
