Abstract：
BACKGROUND: In 2017, the Food and Drug Administration approved pembrolizumab for treatment of any mismatch repair-deficient (dMMR) tumor making MMR immunohistochemistry (IHC) testing beneficial for all tumor types. For the first time, MMR IHC was not performed exclusively to screen for Lynch syndrome (LS).
METHODS: In this study, all MMR IHC reports issued between 2017 and 2021 at an academic hospital were reviewed and completion of genetic testing was determined through chart review. Colorectal cancers (CRCs), endometrial cancers (ECs), and noncancerous lesions were excluded.
RESULTS: Between 2017 and 2021, MMR IHC was completed in 1939 patients with a malignancy other than CRC or EC. Absent or weak staining for at least one MMR protein was detected in 115 (5.9%) patients and 59 (51%) of those completed germline genetic testing. Overall, the identification rate of LS in this cohort was 0.72%, which is similar to the rate in our previously reported CRC and EC universal screening cohort. A diagnosis of LS was most commonly made in patients with dMMR brain (18.75%) and small intestinal cancers (10.20%). Five additional patients were found to carry a pathogenic variant in a non-LS gene.
CONCLUSIONS: Pan-cancer MMR testing for pembrolizumab consideration can identify LS cases at a rate similar to universal CRC and EC screening programs. A persistent challenge is subsequent uptake of genetic testing. MMR testing should be prioritized in brain and small intestinal tumors, and multigene panel testing is recommended in patients with dMMR, as unexpected pathogenic variants in non-LS genes were found as frequently as LS gene variants.
METHODS: In this study, all MMR IHC reports issued between 2017 and 2021 at an academic hospital were reviewed and completion of genetic testing was determined through chart review. Colorectal cancers (CRCs), endometrial cancers (ECs), and noncancerous lesions were excluded.
RESULTS: Between 2017 and 2021, MMR IHC was completed in 1939 patients with a malignancy other than CRC or EC. Absent or weak staining for at least one MMR protein was detected in 115 (5.9%) patients and 59 (51%) of those completed germline genetic testing. Overall, the identification rate of LS in this cohort was 0.72%, which is similar to the rate in our previously reported CRC and EC universal screening cohort. A diagnosis of LS was most commonly made in patients with dMMR brain (18.75%) and small intestinal cancers (10.20%). Five additional patients were found to carry a pathogenic variant in a non-LS gene.
CONCLUSIONS: Pan-cancer MMR testing for pembrolizumab consideration can identify LS cases at a rate similar to universal CRC and EC screening programs. A persistent challenge is subsequent uptake of genetic testing. MMR testing should be prioritized in brain and small intestinal tumors, and multigene panel testing is recommended in patients with dMMR, as unexpected pathogenic variants in non-LS genes were found as frequently as LS gene variants.
摘要：
背景：2017年，美国食品和药物管理局批准pembrolizumab用于治疗任何错配修复缺陷（dMMR）肿瘤，这使得MMR免疫组织化学（IHC）测试对所有肿瘤类型都有益。第一次,MMRIHC并非专门用于筛查Lynch综合征（LS）。
方法：在本研究中，我们对2017年至2021年间在一家学术医院发布的所有MMRIHC报告进行了审查,并通过图表审查确定了基因检测的完成情况.结直肠癌（CRC），子宫内膜癌（EC），和非癌性病变被排除。
结果：在2017年至2021年之间，在1939例非CRC或EC的恶性肿瘤患者中完成了MMRIHC。在115名（5.9％）患者和59名（51％）完成种系遗传检测的患者中，至少一种MMR蛋白的染色缺失或弱染色。总的来说,该队列中LS的识别率为0.72%，这与我们先前报道的CRC和EC通用筛查队列中的比率相似.LS的诊断最常见于dMMR脑癌(18.75%)和小肠癌(10.20%)患者。发现另外五名患者在非LS基因中携带致病性变体。
结论：用于pembrolizumab的泛癌症MMR检测可以以类似于通用CRC和EC筛查计划的速率识别LS病例。一个持续的挑战是随后的基因检测。MMR检测应优先用于脑和小肠肿瘤，dMMR患者建议进行多基因小组检测，因为非LS基因中意外的致病变异与LS基因变异一样频繁。
方法：在本研究中，我们对2017年至2021年间在一家学术医院发布的所有MMRIHC报告进行了审查,并通过图表审查确定了基因检测的完成情况.结直肠癌（CRC），子宫内膜癌（EC），和非癌性病变被排除。
结果：在2017年至2021年之间，在1939例非CRC或EC的恶性肿瘤患者中完成了MMRIHC。在115名（5.9％）患者和59名（51％）完成种系遗传检测的患者中，至少一种MMR蛋白的染色缺失或弱染色。总的来说,该队列中LS的识别率为0.72%，这与我们先前报道的CRC和EC通用筛查队列中的比率相似.LS的诊断最常见于dMMR脑癌(18.75%)和小肠癌(10.20%)患者。发现另外五名患者在非LS基因中携带致病性变体。
结论：用于pembrolizumab的泛癌症MMR检测可以以类似于通用CRC和EC筛查计划的速率识别LS病例。一个持续的挑战是随后的基因检测。MMR检测应优先用于脑和小肠肿瘤，dMMR患者建议进行多基因小组检测，因为非LS基因中意外的致病变异与LS基因变异一样频繁。
