Mismatch repair deficiency: how reliable is the two-antibody approach? A national real-life study

IF 3.9 2区医学 Q2 CELL BIOLOGY

Histopathology Pub Date : 2024-06-11 DOI:10.1111/his.15236

Elisa Vink-Börger, Michael den Bakker, Rinus Voorham, Francien van Nederveen, Iris Nagtegaal

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Abstract

Aims

Traditionally, mismatch repair (MMR) status is determined by a panel of four antibodies (MLH1, PMS2, MSH2, MSH6). If all proteins are retained, cases are MMR proficient (pMMR), while loss of one or more proteins is indicative of MMR deficiency (dMMR). This approach has been challenged in favour of a two-antibody approach, using PMS2 and MSH6 as a first screening. Their retainment is deemed sufficient to declare cases pMMR. In this study we aim to verify the validity of the two-antibody approach.

Methods and Results

We performed a nationwide study in colorectal cancer (CRC) and endometrial cancer (EC) diagnosed between 2016 and 2023, including 47,657 patients to evaluate the two-antibody approach. In 0.17% and 0.4% of cases of CRC and EC, respectively, dMMR cases would be missed with the two-antibody approach. Subgroup analyses pointed towards slightly increased miss rates in younger patients (under the age of 50 years) in both groups and identified special subtypes (signet ring cell carcinoma, medullary carcinoma, and mucinous carcinoma in CRC and clear cell carcinoma in EC) with increased miss rates. For these specific subgroups, a low threshold should be used for further testing. In case of ambiguous or heterogeneous staining patterns, four antibodies should be used.

Conclusion

In general, the application of a two-antibody MMR testing strategy does not lead to considerable failure of dMMR identification and saves costs.

Abstract Image

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错配修复缺陷：双抗体法有多可靠？一项全国真实生活研究。

目的：传统上，错配修复（MMR）状态是通过四种抗体（MLH1、PMS2、MSH2、MSH6）来确定的。如果所有蛋白都保留下来，则病例具有错配修复能力（pMMR），而丢失一种或多种蛋白则表明缺乏错配修复能力（dMMR）。这种方法已受到质疑，而采用了双抗体方法，即使用 PMS2 和 MSH6 作为首次筛选。它们的保留被认为足以宣布病例为 pMMR。本研究旨在验证双抗体方法的有效性：我们在全国范围内对 2016 年至 2023 年期间确诊的结直肠癌（CRC）和子宫内膜癌（EC）进行了研究，包括 47657 名患者，以评估双抗体方法。采用双抗体方法，分别有 0.17% 和 0.4% 的 CRC 和 EC 病例会漏诊 dMMR 病例。亚组分析表明，两组中年轻患者（50 岁以下）的漏诊率略有增加，并发现了漏诊率增加的特殊亚型（CRC 中的标志环细胞癌、髓样癌和粘液癌，EC 中的透明细胞癌）。对于这些特殊亚组，应采用低阈值进行进一步检测。如果染色模式不明确或不均匀，则应使用四种抗体：总的来说，采用双抗体 MMR 检测策略不会导致大量 dMMR 鉴定失败，并能节省成本。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Histopathology 医学-病理学

CiteScore

10.20

自引率

4.70%

发文量

239

审稿时长

1 months

期刊介绍： Histopathology is an international journal intended to be of practical value to surgical and diagnostic histopathologists, and to investigators of human disease who employ histopathological methods. Our primary purpose is to publish advances in pathology, in particular those applicable to clinical practice and contributing to the better understanding of human disease.

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