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Clinical features and impact of p53 status on sporadic mismatch repair deficiency and Lynch syndrome in uterine cancer.
- Source :
-
Cancer science [Cancer Sci] 2024 May; Vol. 115 (5), pp. 1646-1655. Date of Electronic Publication: 2024 Mar 03. - Publication Year :
- 2024
-
Abstract
- The clinical features of sporadic mismatch repair deficiency (MMRd) and Lynch syndrome (LS) in Japanese patients with endometrial cancer (EC) were examined by evaluating the prevalence and prognostic factors of LS and sporadic MMRd in patients with EC. Targeted sequencing of five LS susceptibility genes (MLH1, MSH2, MSH6, PMS2, and EPCAM) was carried out in 443 patients with EC who were pathologically diagnosed with EC at the National Cancer Center Hospital between 2011 and 2018. Pathogenic variants in these genes were detected in 16 patients (3.7%). Immunohistochemistry for MMR proteins was undertaken in 337 of the 433 (77.9%) EC patients, and 91 patients (27.0%) showed absent expression of at least one MMR protein. The 13 cases of LS with MMR protein loss (93.8%) showed a favorable prognosis with a 5-year overall survival (OS) rate of 100%, although there was no statistically significant difference between this group and the sporadic MMRd group (pā=ā0.27). In the MMRd without LS group, the 5-year OS rate was significantly worse in seven patients with an aberrant p53 expression pattern than in those with p53 WT (53.6% vs. 93.9%, log-rank test; pā=ā0.0016). These results suggest that p53 abnormalities and pathogenic germline variants in MMR genes could be potential biomarkers for the molecular classification of EC with MMRd.<br /> (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Female
Humans
Middle Aged
DNA-Binding Proteins genetics
Epithelial Cell Adhesion Molecule genetics
Epithelial Cell Adhesion Molecule metabolism
Japan
Mismatch Repair Endonuclease PMS2 genetics
MutL Protein Homolog 1 genetics
MutS Homolog 2 Protein genetics
Prognosis
Colorectal Neoplasms, Hereditary Nonpolyposis genetics
Colorectal Neoplasms, Hereditary Nonpolyposis pathology
DNA Mismatch Repair genetics
Endometrial Neoplasms genetics
Endometrial Neoplasms pathology
Tumor Suppressor Protein p53 genetics
Uterine Neoplasms genetics
Uterine Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1349-7006
- Volume :
- 115
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cancer science
- Publication Type :
- Academic Journal
- Accession number :
- 38433331
- Full Text :
- https://doi.org/10.1111/cas.16121