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Clinicopathological characteristics and loss of mismatch repair protein expression in Chinese upper tract urothelial carcinomas

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...

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Autores principales: Shang, Zhi, Jin, Shengming, Wang, Wenwen, Wei, Yu, Gu, Chengyuan, Yang, Chen, Zhu, Yu, Zhu, Yao, Shen, Yijun, Wu, Junlong, Ye, Dingwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9640928/
https://www.ncbi.nlm.nih.gov/pubmed/36387191
http://dx.doi.org/10.3389/fonc.2022.1012168
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author Shang, Zhi
Jin, Shengming
Wang, Wenwen
Wei, Yu
Gu, Chengyuan
Yang, Chen
Zhu, Yu
Zhu, Yao
Shen, Yijun
Wu, Junlong
Ye, Dingwei
author_facet Shang, Zhi
Jin, Shengming
Wang, Wenwen
Wei, Yu
Gu, Chengyuan
Yang, Chen
Zhu, Yu
Zhu, Yao
Shen, Yijun
Wu, Junlong
Ye, Dingwei
author_sort Shang, Zhi
collection PubMed
description 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.
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spelling pubmed-96409282022-11-15 Clinicopathological characteristics and loss of mismatch repair protein expression in Chinese upper tract urothelial carcinomas Shang, Zhi Jin, Shengming Wang, Wenwen Wei, Yu Gu, Chengyuan Yang, Chen Zhu, Yu Zhu, Yao Shen, Yijun Wu, Junlong Ye, Dingwei Front Oncol Oncology 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. Frontiers Media S.A. 2022-10-25 /pmc/articles/PMC9640928/ /pubmed/36387191 http://dx.doi.org/10.3389/fonc.2022.1012168 Text en Copyright © 2022 Shang, Jin, Wang, Wei, Gu, Yang, Zhu, Zhu, Shen, Wu and Ye https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Shang, Zhi
Jin, Shengming
Wang, Wenwen
Wei, Yu
Gu, Chengyuan
Yang, Chen
Zhu, Yu
Zhu, Yao
Shen, Yijun
Wu, Junlong
Ye, Dingwei
Clinicopathological characteristics and loss of mismatch repair protein expression in Chinese upper tract urothelial carcinomas
title Clinicopathological characteristics and loss of mismatch repair protein expression in Chinese upper tract urothelial carcinomas
title_full Clinicopathological characteristics and loss of mismatch repair protein expression in Chinese upper tract urothelial carcinomas
title_fullStr Clinicopathological characteristics and loss of mismatch repair protein expression in Chinese upper tract urothelial carcinomas
title_full_unstemmed Clinicopathological characteristics and loss of mismatch repair protein expression in Chinese upper tract urothelial carcinomas
title_short Clinicopathological characteristics and loss of mismatch repair protein expression in Chinese upper tract urothelial carcinomas
title_sort clinicopathological characteristics and loss of mismatch repair protein expression in chinese upper tract urothelial carcinomas
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9640928/
https://www.ncbi.nlm.nih.gov/pubmed/36387191
http://dx.doi.org/10.3389/fonc.2022.1012168
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