Validity of a two-antibody testing algorithm for mismatch repair deficiency testing in cancer; a systematic literature review and meta-analysis.
Validity of a two-antibody testing algorithm for mismatch repair deficiency testing in cancer; a systematic literature review and meta-analysis.
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DOI：
10.1038/s41379-022-01149-w
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发表时间：
2022-12
期刊：
影响因子：
7.5
通讯作者：
Bosse, T.
中科院分区：
文献类型：
--
作者：
Aiyer, K. T. S.;Doeleman, T.;Ryan, N. A.;Nielsen, M.;Crosbie, E. J.;Smit, V. T. H. B. M.;Morreau, H.;Goeman, J. J.;Bosse, T.
MLH1、PMS2、MSH2 和 MSH6 的反射错配修复免疫组织化学 (MMR IHC) 检测用于筛查林奇综合征。最近，MMR 缺陷 (MMRd) 已被批准作为检查点抑制剂治疗的泛癌预测生物标志物，导致 MMR IHC 在临床实践中的使用大幅增加。我们探讨了 PMS2 和 MSH6 免疫组织化学染色是否可以作为可靠的替代品。这种二抗检测算法具有节省组织、降低成本和节省时间的优点。系统地检索了 PubMed、Embase 和 Cochrane 图书馆报告 MMR IHC 的文章。使用 R 中的随机效应模型荟萃分析，对单独 MLH1 或 MSH2 丢失或仅合并 MLH1/MSH2 丢失的病例的加权百分比进行分析。搜索产生了 1704 个独特的引用，其中纳入了 131 项研究，描述了 9014 名患者。观察到单独 MLH1 或 MSH2 丢失或仅联合 MLH1/MSH2 丢失的病例的加权百分比为 1.1%（95% CI 0.53–18.87，I = 87%）。在以研究二抗检测算法为主要目的的六篇文章中，所有 MMRd 病例均通过二抗检测算法检测到，没有单独 MLH1 或 MSH2 丢失或单独联合 MLH1/MSH2 丢失的病例。二抗检测算法对 MMRd 的高检出率支持了专业病理学家在临床实践中的使用。在两种抗体测试算法结果模棱两可的情况下，所有四种抗体的染色仍应作为标准。最后，讨论染色图案陷阱的教育课程将仍然很重要。
Reflex mismatch repair immunohistochemistry (MMR IHC) testing for MLH1, PMS2, MSH2 and MSH6 is used to screen for Lynch syndrome. Recently MMR-deficiency (MMRd) has been approved as a pan-cancer predictive biomarker for checkpoint inhibitor therapy, leading to a vast increase in the use of MMR IHC in clinical practice. We explored whether immunohistochemical staining with PMS2 and MSH6 can be used as a reliable substitute. This two-antibody testing algorithm has the benefit of saving tissue, cutting costs and saving time. PubMed, Embase and Cochrane library were systematically searched for articles reporting on MMR IHC. The weighed percentage of cases with isolated MLH1 or MSH2 loss or combined MLH1/MSH2 loss alone was analyzed using a random effects model meta-analysis in R. The search yielded 1704 unique citations, of which 131 studies were included, describing 9014 patients. A weighed percentage of 1.1% (95% CI 0.53–18.87, I = 87%) of cases with isolated MLH1 or MSH2 loss or combined MLH1/MSH2 loss alone was observed. In the six articles with the main aim of investigating the two-antibody testing algorithm all MMRd cases were detected with the two-antibody testing algorithm, there were no cases with isolated MLH1 or MSH2 loss or combined MLH1/MSH2 loss alone. This high detection rate of MMRd of the two-antibody testing algorithm supports its use in clinical practice by specialized pathologists. Staining of all four antibodies should remain the standard in cases with equivocal results of the two-antibody testing algorithm. Finally, educational sessions in which staining pattern pitfalls are discussed will continue to be important.
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