Diffuse sclerosing variant of papillary thyroid carcinoma: major genetic alterations and prognostic implications
Diffuse sclerosing variant of papillary thyroid carcinoma: major genetic alterations and prognostic implications
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DOI：
10.1111/his.12902
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发表时间：
2016-07-01
期刊：
影响因子：
6.4
通讯作者：
Kim, Sun W.
中科院分区：
文献类型：
--
作者：
Joung, Ji Y.;Kim, Tae H.;Kim, Sun W.
目的弥漫性硬化变甲状腺乳头状癌（DSV-PTC）是一种罕见的甲状腺乳头状癌，其预后意义尚存争议。本研究的目的是探讨DSV-PTC的主要遗传改变及其预后意义。方法和结果我们纳入37例甲状腺手术的DSV-PTC患者，并进行了福尔马林固定石蜡包埋样品。我们使用逆转录实时聚合酶链反应（PCR）检测了一组遗传改变，包括BRAF（V600E）、NRAS密码子61、HRAS密码子12/13/61和KRAS密码子12/13点突变以及RET/PTC1、RET/PTC3和PAX8/PPAR重排。PCR发现的所有基因改变均经Sanger测序证实。评估鉴定的遗传改变与临床病理特征之间的关系。37例DSV-PTC中，RET/PTC1阳性17例（46%），RET/PTC3阳性6例（16%），BRAF（V600E）阳性9例（24%）。所有的突变/重排都是相互排斥的。其余5例没有上述基因改变。伴有RET/ pt3重排的DSV-PTC与晚期疾病相关，包括T4和远处转移（P < 0.05）。RET/PTC3患者出现持续性疾病的频率较高（P < 0.01）。相比之下，DSV-PTC合并RET/PTC1与更高的疾病缓解率（P < 0.05）和共存的桥本甲状腺炎（P < 0.01）相关。综上所述，RET/PTC重排是DSV-PTC患者的主要基因改变，RET/PTC重排与诊断晚期和临床预后差有关。
AimDiffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is an uncommon variant of PTC, and its prognostic significance remains controversial. The aim of this study was to investigate the major genetic alterations of DSV-PTC and their prognostic implications.Methods and resultsWe included 37 patients with DSV-PTC who underwent thyroid surgery and had formalin-fixed paraffin-embedded samples. We tested for a panel of genetic alterations, including BRAF(V600E), NRAS codon 61, HRAS codon 12/13/61 and KRAS codon 12/13 point mutations as well as RET/PTC1, RET/PTC3 and PAX8/PPAR rearrangements using reverse transcription real-time polymerase chain reaction (PCR). All genetic alterations found on PCR were confirmed by Sanger sequencing. Associations between the identified genetic alterations and clinicopathological characteristics were evaluated. Among 37 cases of DSV-PTC, 17 were positive for RET/PTC1 (46%), six for RET/PTC3 (16%) and nine for BRAF(V600E) (24%). All mutations/rearrangements were mutually exclusive. The remaining five cases had none of the above genetic alterations. DSV-PTC with RET/PTC3 rearrangement was associated with advanced-stage disease, including T4 and distant metastasis (P < 0.05). Patients with RET/PTC3 showed a higher frequency of persistent disease (P < 0.01). In contrast, DSV-PTC with RET/PTC1 was associated with a higher prevalence of disease remission (P < 0.05) and coexistent Hashimoto's thyroiditis (P < 0.01).ConclusionTaken together, RET/PTC rearrangement was the major genetic alteration seen in patients with DSV-PTC, and the RET/PTC3 rearrangement was associated with advanced stage at diagnosis and poor clinical outcome.