Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Department of Obstetrics and Gynecology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Asian Pac J Cancer Prev. 2024 Oct 1;25(10):3667-3671. doi: 10.31557/APJCP.2024.25.10.3667.
Mismatch repair deficiency (dMMR) is a well-established characteristic of endometrial adenocarcinoma and is crucial in screening for Lynch syndrome, guiding adjuvant treatment decisions, and identifying candidates for immune checkpoint inhibitors. The traditional approach to dMMR screening involves a four-antibody panel, but a simplified two-antibody method utilizing PMS2 and MSH6 has shown promise. This study aims to compare the diagnostic performance of the simplified two-antibody method with the traditional four-antibody panel in endometrial cancer samples.
We conducted a retrospective cohort study on endometrial carcinoma cases diagnosed between 2013 and 2022. We compared the diagnostic performance of the two-antibody panel with the traditional four-antibody panel in detecting dMMR. Clinical data and immunohistochemistry results were collected, and agreement between the two methods was evaluated using Cohen's kappa coefficient.
304 endometrial cancer cases were included, with 27% demonstrating loss of at least one MMR protein using the four-antibody panel. The two-antibody method detected MMR deficiency in 26.6% of cases, with a high agreement rate of 98.8% between the two methods. Only one case showed discordant results, prompting further investigation.
The simplified two-antibody MMR IHC screening approach using PMS2 and MSH6 showed high concordance with the traditional four-antibody panel. This suggests its potential as an alternative method for reflex MMR status testing in endometrial adenocarcinoma. The implementation of this approach could streamline the diagnostic process, reduce costs, and improve the detection of Lynch syndrome in affected individuals and their families. Further studies with larger cohorts and long-term follow-up are needed to validate these findings and assess the clinical implications of this approach in routine practice.
错配修复缺陷（dMMR）是子宫内膜腺癌的一个明确特征，对于林奇综合征的筛查、辅助治疗决策的指导以及免疫检查点抑制剂候选者的识别至关重要。传统的 dMMR 筛选方法涉及四抗面板，但使用 PMS2 和 MSH6 的简化两抗方法显示出了前景。本研究旨在比较简化两抗方法与传统四抗面板在子宫内膜癌样本中的诊断性能。
我们对 2013 年至 2022 年间诊断的子宫内膜癌病例进行了回顾性队列研究。我们比较了两抗面板与传统四抗面板在检测 dMMR 中的诊断性能。收集了临床数据和免疫组化结果，并使用 Cohen's kappa 系数评估了两种方法之间的一致性。
纳入了 304 例子宫内膜癌病例，其中 27%的病例使用四抗面板显示至少一种 MMR 蛋白缺失。两抗方法检测到 26.6%的病例存在 MMR 缺陷，两种方法之间的一致性率高达 98.8%。仅一个病例显示出不一致的结果，需要进一步调查。
使用 PMS2 和 MSH6 的简化两抗 MMR IHC 筛选方法与传统四抗面板具有高度一致性。这表明它可能是子宫内膜腺癌中用于反射性 MMR 状态检测的替代方法。实施这种方法可以简化诊断过程，降低成本，并提高对受影响个体及其家族中林奇综合征的检测率。需要进一步的研究，包括更大的队列和长期随访，以验证这些发现，并评估这种方法在常规实践中的临床意义。
