Shang Zhi, Jin Shengming, Wang Wenwen, Wei Yu, Gu Chengyuan, Yang Chen, Zhu Yu, Zhu Yao, Shen Yijun, Wu Junlong, Ye Dingwei
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Front Oncol. 2022 Oct 25;12:1012168. doi: 10.3389/fonc.2022.1012168. eCollection 2022.
Expression of DNA mismatch repair (MMR) protein (MLH1, PMS2, MSH2, and MSH6) in upper tract urothelial carcinoma (UTUC) has been explored in Western cohorts, but it is rarely reported in Eastern cohorts. We aimed to assess the loss of MMR protein expression among Chinese UTUC patients and study its clinicopathological implications. We enrolled 175 UTUC patients at our center and tested the expression of MMR proteins by immunohistochemistry. Then, we explored these patients' clinicopathological characteristics. We found loss of MMR proteins in 19 (10.9%) of 175 patients in our cohort (6 MSH2 and MSH6, 2 MSH6 alone, 6 MSH2 alone, 3 MLH1 and PMS2, and 2 PMS2 alone). Loss of MMR proteins was not a significant prognostic factor of relapse-free survival for these patients. In addition, patients with lower T stage or with bladder cancer history were more likely to have loss of MMR protein expression. At last, two metastatic patients (MSH2 and MSH6 loss; MSH2 loss) with loss of MMR protein experienced tumor recession after several cycles of anti-PD-1 immunotherapy. In conclusion, this is the largest Chinese UTUC cohort study to date that explores the loss of MMR protein expression. The rate of MMR loss observed was comparable to that in the Western UTUC cohort, supporting universal UTUC screening in China. Furthermore, a subset of advanced UTUCs with MMR protein loss are probably immunogenic, for whom single or combined immunotherapy may be potential therapeutic options in the future.
西方队列研究已对DNA错配修复（MMR）蛋白（MLH1、PMS2、MSH2和MSH6）在上尿路尿路上皮癌（UTUC）中的表达进行了探索，但在东方队列中鲜有报道。我们旨在评估中国UTUC患者中MMR蛋白表达缺失情况，并研究其临床病理意义。我们纳入了本中心的175例UTUC患者，通过免疫组织化学检测MMR蛋白的表达。然后，我们探究了这些患者的临床病理特征。我们发现，在我们的队列中，175例患者中有19例（10.9%）出现MMR蛋白缺失（6例MSH2和MSH6缺失，2例仅MSH6缺失，6例仅MSH2缺失，3例MLH1和PMS2缺失，2例仅PMS2缺失）。MMR蛋白缺失并非这些患者无复发生存的显著预后因素。此外，T分期较低或有膀胱癌病史的患者更有可能出现MMR蛋白表达缺失。最后，两名MMR蛋白缺失的转移性患者（MSH2和MSH6缺失；MSH2缺失）在接受几个周期的抗PD-1免疫治疗后肿瘤出现退缩。总之，这是迄今为止探索MMR蛋白表达缺失的最大规模中国UTUC队列研究。观察到的MMR缺失率与西方UTUC队列相当，支持在中国进行普遍的UTUC筛查。此外，一部分MMR蛋白缺失的晚期UTUC可能具有免疫原性，未来单药或联合免疫治疗可能是其潜在的治疗选择。
