Gou Qiheng, Xie Yuxin, Zhang Mengni, Chen Ye, Shen Yali
Department of Head and Neck Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Department of Pathology, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Cancer Manag Res. 2021 Oct 21;13:8009-8015. doi: 10.2147/CMAR.S333690. eCollection 2021.
The increasingly widespread use of immunohistochemistry and next-generation sequencing (NGS) in the detection of microsatellite instability (MSI) and DNA mismatch repair (MMR) status has led to the observation of various unusual tumour types that exhibit MMR protein deficiency in Lynch syndrome (LS). Here, we report a case of two synchronous colorectal cancer (CRC) tumours simultaneously occurring in a 42-year-old woman with a deleterious germline mutation in MSH6, abundant expression of PD-L1 and high tumour mutation burden (TMB). The two CRC tumours (tumours A and B) harboured highly heterogeneous features. One showed loss of MSH6 protein and a microsatellite stable (MSS)/MSI-low (MSI-L) status, while the other presented no loss of MMR protein and MSI-H status. Furthermore, the 9 common mutated genes between the two CRC tumours had no shared mutation sites. Only 4 KEGG pathways were identified as enriched for five of the common mutated genes, while 8 cancer-related pathways were identified as enriched for 9 and 13 unique mutated genes in tumours A and B, respectively. Therefore, we chose immune checkpoint inhibitors (ICIs) as the potential therapy. This case exemplifies the complexity of tumorigenesis and potential ICI treatment in LS patients.
免疫组织化学和下一代测序（NGS）在检测微卫星不稳定性（MSI）和DNA错配修复（MMR）状态方面的应用日益广泛，这使得人们观察到林奇综合征（LS）中出现的各种表现为MMR蛋白缺陷的不寻常肿瘤类型。在此，我们报告一例42岁女性同时发生的两例同步性结直肠癌（CRC）肿瘤病例，该女性携带MSH6有害种系突变、PD-L1表达丰富且肿瘤突变负荷（TMB）高。这两例CRC肿瘤（肿瘤A和肿瘤B）具有高度异质性特征。其中一例显示MSH6蛋白缺失且为微卫星稳定（MSS）/微卫星低度不稳定（MSI-L）状态，而另一例则未出现MMR蛋白缺失且为微卫星高度不稳定（MSI-H）状态。此外，这两例CRC肿瘤之间的9个常见突变基因没有共同的突变位点。仅发现4条KEGG通路在5个常见突变基因中富集，而分别发现8条与癌症相关的通路在肿瘤A和肿瘤B中的9个和13个独特突变基因中富集。因此，我们选择免疫检查点抑制剂（ICI）作为潜在治疗方法。该病例体现了LS患者肿瘤发生的复杂性以及ICI治疗的潜力。
