通过免疫组织化学检测DNA错配修复（MMR）缺陷可有效诊断子宫内膜癌中的微卫星不稳定性（MSI）表型。

Detection of DNA mismatch repair (MMR) deficiencies by immunohistochemistry can effectively diagnose the microsatellite instability (MSI) phenotype in endometrial carcinomas.

作者信息

McConechy M K, Talhouk A, Li-Chang H H, Leung S, Huntsman D G, Gilks C B, McAlpine J N

机构信息

Department of Pathology and Laboratory Medicine, University of British Columbia and BC Cancer Agency, 509-2660 Oak Street, Vancouver V6H 3Z6, BC, Canada.

Genetic Pathology Evaluation Centre, Department of Pathology and Laboratory Medicine, University of British Columbia, 509-2660 Oak Street, Vancouver V6H 3Z6, BC, Canada.

出版信息

Gynecol Oncol. 2015 May;137(2):306-10. doi: 10.1016/j.ygyno.2015.01.541. Epub 2015 Jan 28.

DOI:10.1016/j.ygyno.2015.01.541

PMID:25636458

Abstract

BACKGROUND

A proportion of endometrial carcinomas (ECs) are associated with deficient DNA mismatch repair (MMR). These tumors are characterized by high levels of microsatellite instability (MSI). Identification of MSI is important in identifying women who should be tested for Lynch syndrome and identifying a phenotype that may have specific prognostic and predictive implications. Genomic characterization of ECs has shown that MSI tumors form a distinct subgroup. The two most common methodologies for MSI assessment have not been compared in EC.

METHODS

Pentaplex mono and di-nucleotide PCR for MSI testing was compared to MMR IHC (presence/absence of MLH1, MSH2, MSH6, PMS2) in a cohort of patients with EC. Concordance, Kappa statistic, sensitivity, specificity, positive and negative predictive values were obtained on the cross-tabulation of results.

RESULTS

Comparison of both MSI and MMR status was complete for 89 cases. Overall agreement between methods (concordance) was 93.3% (95% CI[85.9%-97.5%]). A one-sided test to determine whether the accuracy is better than the "no information rate," which is taken to be the largest class percentage in the data, is significant (p<0.00001). Unweighted Kappa was 0.84, along with the sensitivity (88.5%), specificity (95.2%), PPV (88.5%), and NPV (95.2%). The balanced accuracy (i.e. the average between sensitivity and specificity) was 92%.

DISCUSSION

We show the equivalence of MSI testing and MMR IHC. We advocate the implementation of MMR IHC in future EC classification schemes, enabling stratification of cases for future clinical trials as well as assisting identification of Lynch syndrome, so that screening and risk reducing interventions can be undertaken.

摘要

背景

一部分子宫内膜癌（EC）与DNA错配修复（MMR）缺陷有关。这些肿瘤的特征是微卫星不稳定性（MSI）水平高。MSI的识别对于确定应进行林奇综合征检测的女性以及识别可能具有特定预后和预测意义的表型很重要。EC的基因组特征表明，MSI肿瘤形成一个独特的亚组。在EC中尚未比较两种最常用的MSI评估方法。

方法

在一组EC患者中，将用于MSI检测的五重单核苷酸和双核苷酸PCR与MMR免疫组化（MLH1、MSH2、MSH6、PMS2的存在/缺失）进行比较。通过结果的交叉表获得一致性、Kappa统计量、敏感性、特异性、阳性和阴性预测值。

结果

89例患者的MSI和MMR状态比较全部完成。两种方法之间的总体一致性（一致性）为93.3%（95%CI[85.9%-97.5%]）。用于确定准确性是否优于“无信息率”（即数据中最大的类别百分比）的单侧检验具有显著性（p<0.00001）。未加权Kappa为0.84，敏感性为88.5%，特异性为95.2%，PPV为88.5%，NPV为95.2%。平衡准确性（即敏感性和特异性的平均值）为92%。