Differential outcomes and immune checkpoint inhibitor response among endometrial cancer patients with MLH1 hypermethylation versus MLH1 “Lynch-like” mismatch repair gene mutation

To identify differential survival outcomes and immune checkpoint inhibitor (ICI) response in MLH1 hypermethylated versus MLH1 mutated (“Lynch-like”) endometrial tumors and determine whether their molecular profiles can elucidate the differential outcomes. 1673 mismatch repair deficient endometrial t...

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Bibliographic Details
Published in:Gynecologic oncology 2023-10, Vol.177, p.132-141
Main Authors: Toboni, Michael D., Wu, Sharon, Farrell, Alex, Xiu, Joanne, Ribeiro, Jennifer R., Oberley, Matthew J., Arend, Rebecca, Erickson, Britt K., Herzog, Thomas J., Thaker, Premal H., Powell, Matthew A.
Format: Article
Language:English
Subjects:
Endometrial cancer
Hormonal therapy
Immune microenvironment
Immunotherapy
Mismatch repair deficiency
MLH1 hypermethylation
MLH1 mutation
Molecular profiling
Precision oncology
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Summary:To identify differential survival outcomes and immune checkpoint inhibitor (ICI) response in MLH1 hypermethylated versus MLH1 mutated (“Lynch-like”) endometrial tumors and determine whether their molecular profiles can elucidate the differential outcomes. 1673 mismatch repair deficient endometrial tumors were analyzed by next-generation sequencing and whole transcriptome sequencing (Caris Life Sciences, Phoenix, AZ). PD-L1, ER, and PR were tested by immunohistochemistry and immune cell infiltrates were calculated using MCP-counter. Significance was determined using Chi-square and Mann-Whitney U tests and adjusted for multiple comparisons. Overall survival (OS) was depicted using Kaplan-Meier survival curves. The endometrial cancer cohort comprised 89.2% patients with MLH1 hypermethylated tumors and 10.8% with MLH1 mutated tumors, with median ages of 67 and 60 years, respectively (p 
ISSN:0090-8258
1095-6859
DOI:10.1016/j.ygyno.2023.08.015