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免疫组织化学不能替代DNA分析用于评估甲状腺乳头状癌中的V600E突变。

Immunohistochemistry cannot replace DNA analysis for evaluation of V600E mutations in papillary thyroid carcinoma.

作者信息

Szymonek Monika, Kowalik Artur, Kopczyński Janusz, Gąsior-Perczak Danuta, Pałyga Iwona, Walczyk Agnieszka, Gadawska-Juszczyk Klaudia, Płusa Agnieszka, Mężyk Ryszard, Chrapek Magdalena, Góźdź Stanisław, Kowalska Aldona

机构信息

Endocrinology Clinic, Holycross Cancer Center, Kielce, Poland.

Department of Molecular Diagnostics, Holycross Cancer Center, Kielce, Poland.

出版信息

Oncotarget. 2017 Aug 24;8(43):74897-74909. doi: 10.18632/oncotarget.20451. eCollection 2017 Sep 26.

Abstract

INTRODUCTION

The V600E mutation is the most common genetic event occurring in papillary thyroid cancer (PTC). Recently, the possibility of using immunohistochemistry (IHC) to detect the V600E mutation has been reported.

MATERIALS AND METHODS

In 140 patients with classical PTC, the status of the V600E mutation was determined by IHC (using two alternative staining protocols, IHC-1 and IHC-2) and molecular biology methods: Sanger sequencing (SEQ) and real-time PCR (qPCR).

RESULTS

The V600E mutation was detected in 57.1% (80/140) patients by IHC-1 and 62.9% (88/140) patients by IHC-2. The highest correlation in detecting the V600E mutation was found between IHC-2 and qPCR (94.2%), and between IHC-1 and qPCR (83.9%). Correlations between IHC-1 and SEQ and between IHC-2 and SEQ were 71.5% and 76.2%, respectively. The IHC-2 protocol had higher sensitivity, PPV, and NPV, and Cohen's kappa than IHC- 1. The presence of V600E mutation in IHC-2 statistically correlated with age at diagnosis, histopathological stage, and extrathyroidal extension.

CONCLUSIONS

The results obtained in this study indicate a lack of concordance between V600E detection by IHC and molecular methods. The IHC method cannot replace molecular methods for the detection of the V600E mutation.

摘要

引言

V600E 突变是甲状腺乳头状癌(PTC)中最常见的基因事件。最近,有报道称可利用免疫组织化学(IHC)检测 V600E 突变。

材料与方法

对 140 例经典型 PTC 患者,采用免疫组织化学(使用两种替代染色方案,即 IHC - 1 和 IHC - 2)及分子生物学方法(桑格测序法(SEQ)和实时定量聚合酶链反应(qPCR))来确定 V600E 突变状态。

结果

通过 IHC - 1 检测到 57.1%(80/140)的患者存在 V600E 突变,通过 IHC - 2 检测到 62.9%(88/140)的患者存在该突变。在检测 V600E 突变方面,发现 IHC - 2 与 qPCR 之间的相关性最高(94.2%),IHC - 1 与 qPCR 之间的相关性为 83.9%。IHC - 1 与 SEQ 之间以及 IHC - 2 与 SEQ 之间的相关性分别为 71.5%和 76.2%。与 IHC - 1 相比,IHC - 2 方案具有更高的敏感性、阳性预测值、阴性预测值和 Cohen's kappa 值。IHC - 2 中 V600E 突变的存在与诊断年龄、组织病理学分期及甲状腺外侵犯在统计学上相关。

结论

本研究所得结果表明,免疫组织化学检测 V600E 与分子方法之间缺乏一致性。免疫组织化学方法不能替代分子方法检测 V600E 突变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/651a/5650387/66630a518110/oncotarget-08-74897-g001.jpg

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