Comprehensive analysis of DNA mismatch repair-deficient gastric cancer in a Japanese hospital-based population.
Adult
Aged
Aged, 80 and over
Brain Neoplasms
/ complications
Colorectal Neoplasms
/ complications
Colorectal Neoplasms, Hereditary Nonpolyposis
/ epidemiology
DNA Mismatch Repair
/ genetics
Female
Gene Frequency
Genetic Testing
Hospitalization
/ statistics & numerical data
Hospitals
/ statistics & numerical data
Humans
Immunohistochemistry
Japan
/ epidemiology
Male
Middle Aged
Neoplasm Recurrence, Local
/ genetics
Neoplastic Syndromes, Hereditary
/ complications
Prevalence
Retrospective Studies
Stomach Neoplasms
/ drug therapy
Young Adult
Lynch syndrome
Lynch-like syndrome
anti-PD-1 blockade
defective MMR
gastric cancer
Journal
Japanese journal of clinical oncology
ISSN: 1465-3621
Titre abrégé: Jpn J Clin Oncol
Pays: England
ID NLM: 0313225
Informations de publication
Date de publication:
28 May 2021
28 May 2021
Historique:
received:
28
11
2020
accepted:
04
02
2021
pubmed:
18
3
2021
medline:
8
6
2021
entrez:
17
3
2021
Statut:
ppublish
Résumé
The attention on mismatch repair-deficient (dMMR) gastric cancer has increased in this era of anti-PD-1 blockade therapy; however, the prevalence and molecular genetics of patients with dMMR gastric cancer have not been completely investigated. Immunohistochemistry of MMR proteins (MLH1, MSH2, MSH6 and PMS2) was performed on formalin-fixed paraffin-embedded sections prepared from resected primary gastric cancers of 513 consecutive patients. Genetic and/or epigenetic alterations of the MMR genes were also investigated. Loss of expression of one or more MMR proteins was observed in 58 patients (11.3%); 54 patients showed loss of MLH1/PMS2, 3 patients showed loss of MLH1/PMS2/MSH6 and 1 patient showed loss of PMS2 alone. Among these 58 patients, 55 showed hypermethylation of the promoter region of MLH1. Genetic testing revealed that the remaining three patients had Lynch syndrome (n = 1) or Lynch-like syndrome (n = 2). A total of 15 patients (25.9% of all patients with dMMR gastric cancer and 2.9% of all patients with gastric cancer), including 11 patients with stage I-III dMMR gastric cancer who had recurrence and 4 patients with stage IV dMMR gastric cancer, are potential candidates for the use of anti-PD-1 blockades. This is the first study to investigate the frequency and molecular genetic mechanisms of dMMR gastric cancer comprehensively, focusing on the benefit of using PD-1 blockades. Our observations will be beneficial in the clinical practice of metastatic gastric cancer.
Sections du résumé
BACKGROUND
BACKGROUND
The attention on mismatch repair-deficient (dMMR) gastric cancer has increased in this era of anti-PD-1 blockade therapy; however, the prevalence and molecular genetics of patients with dMMR gastric cancer have not been completely investigated.
METHODS
METHODS
Immunohistochemistry of MMR proteins (MLH1, MSH2, MSH6 and PMS2) was performed on formalin-fixed paraffin-embedded sections prepared from resected primary gastric cancers of 513 consecutive patients. Genetic and/or epigenetic alterations of the MMR genes were also investigated.
RESULTS
RESULTS
Loss of expression of one or more MMR proteins was observed in 58 patients (11.3%); 54 patients showed loss of MLH1/PMS2, 3 patients showed loss of MLH1/PMS2/MSH6 and 1 patient showed loss of PMS2 alone. Among these 58 patients, 55 showed hypermethylation of the promoter region of MLH1. Genetic testing revealed that the remaining three patients had Lynch syndrome (n = 1) or Lynch-like syndrome (n = 2). A total of 15 patients (25.9% of all patients with dMMR gastric cancer and 2.9% of all patients with gastric cancer), including 11 patients with stage I-III dMMR gastric cancer who had recurrence and 4 patients with stage IV dMMR gastric cancer, are potential candidates for the use of anti-PD-1 blockades.
CONCLUSIONS
CONCLUSIONS
This is the first study to investigate the frequency and molecular genetic mechanisms of dMMR gastric cancer comprehensively, focusing on the benefit of using PD-1 blockades. Our observations will be beneficial in the clinical practice of metastatic gastric cancer.
Identifiants
pubmed: 33728435
pii: 6174322
doi: 10.1093/jjco/hyab026
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
886-894Informations de copyright
© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.