Prevalence and molecular characteristics of DNA mismatch repair deficient endometrial cancer in a Japanese hospital-based population.
Adult
Age Distribution
Aged
Aged, 80 and over
Colorectal Neoplasms, Hereditary Nonpolyposis
/ genetics
DNA Methylation
/ genetics
DNA Mismatch Repair
/ genetics
Endometrial Neoplasms
/ epidemiology
Female
Hospitals
Humans
Immunohistochemistry
Japan
/ epidemiology
Middle Aged
MutL Protein Homolog 1
/ genetics
Prevalence
Lynch syndrome
Lynch-like syndrome
colorectal cancer
defective MMR
endometrial 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:
01 Jan 2021
01 Jan 2021
Historique:
received:
24
03
2020
accepted:
20
07
2020
pubmed:
28
8
2020
medline:
15
1
2021
entrez:
27
8
2020
Statut:
ppublish
Résumé
The prevalence and molecular characteristics of defective DNA mismatch repair endometrial cancers in the Japanese population have been underexplored. Data supporting clinical management of patients with Lynch-like syndrome and germline variant of uncertain significance of mismatch repair genes are still lacking. Immunohistochemistry of mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) was performed on formalin-fixed paraffin-embedded sections prepared from resected primary endometrial cancers in 395 women with a median age of 59 years. Genetic and/or epigenetic alterations of the mismatch repair genes were also investigated. Loss of expression of one or more mismatch repair proteins was observed in 68 patients (17.2%). A total of 17 out of 68 patients (25%, 4.3% of all cases) were identified as candidates for genetic testing for Lynch syndrome after excluding 51 patients with MLH1 hypermethylated cancer. Fourteen of these 17 patients subjected to genetic testing were found to have Lynch syndrome (n = 5), germline variant of uncertain significance (n = 2) or Lynch-like syndrome (n = 7). Compared with patients with Lynch syndrome, those with germline variant of uncertain significance and Lynch-like syndrome tended to demonstrate an older age at the time of endometrial cancer diagnosis (P = 0.07), less fulfillment of the revised Bethesda guidelines (P = 0.09) and lower prevalence of Lynch syndrome-associated tumors in their first-degree relatives (P = 0.01). This study provides useful information for management in patients with DNA mismatch repair endometrial cancer. Specifically, cancer surveillance as recommended in patients with Lynch syndrome might not be necessary in patients with germline variant of uncertain significance and Lynch-like syndrome and their relatives.
Sections du résumé
BACKGROUND
BACKGROUND
The prevalence and molecular characteristics of defective DNA mismatch repair endometrial cancers in the Japanese population have been underexplored. Data supporting clinical management of patients with Lynch-like syndrome and germline variant of uncertain significance of mismatch repair genes are still lacking.
METHODS
METHODS
Immunohistochemistry of mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) was performed on formalin-fixed paraffin-embedded sections prepared from resected primary endometrial cancers in 395 women with a median age of 59 years. Genetic and/or epigenetic alterations of the mismatch repair genes were also investigated.
RESULTS
RESULTS
Loss of expression of one or more mismatch repair proteins was observed in 68 patients (17.2%). A total of 17 out of 68 patients (25%, 4.3% of all cases) were identified as candidates for genetic testing for Lynch syndrome after excluding 51 patients with MLH1 hypermethylated cancer. Fourteen of these 17 patients subjected to genetic testing were found to have Lynch syndrome (n = 5), germline variant of uncertain significance (n = 2) or Lynch-like syndrome (n = 7). Compared with patients with Lynch syndrome, those with germline variant of uncertain significance and Lynch-like syndrome tended to demonstrate an older age at the time of endometrial cancer diagnosis (P = 0.07), less fulfillment of the revised Bethesda guidelines (P = 0.09) and lower prevalence of Lynch syndrome-associated tumors in their first-degree relatives (P = 0.01).
CONCLUSIONS
CONCLUSIONS
This study provides useful information for management in patients with DNA mismatch repair endometrial cancer. Specifically, cancer surveillance as recommended in patients with Lynch syndrome might not be necessary in patients with germline variant of uncertain significance and Lynch-like syndrome and their relatives.
Identifiants
pubmed: 32844218
pii: 5897065
doi: 10.1093/jjco/hyaa142
doi:
Substances chimiques
MLH1 protein, human
0
MutL Protein Homolog 1
EC 3.6.1.3
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
60-69Informations de copyright
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