Back to Search Start Over

KRAS mutations in endometrial cancers: Possible prognostic and treatment implications.

KRAS mutations in endometrial cancers: Possible prognostic and treatment implications.

Authors :
Kilowski, Karolina A.
Dietrich, Martin F.
Xiu, Joanne
Baca, Yasmine
Hinton, Andrew
Ahmad, Sarfraz
Herzog, Thomas J.
Thaker, Premal
Holloway, Robert W.
Source :
Gynecologic Oncology. Dec2024, Vol. 191, p299-306. 8p.
Publication Year :
2024

Abstract

Patients with recurrent or metastatic endometrial cancer (EC) have poor prognoses with limited therapeutic options following immunotherapy or immunochemotherapy treatments. Inhibitors of KRAS mutations (KRAS-mut) have shown efficacy in early solid tumor studies, but data in EC are lacking. This study describes the frequency of KRAS-mut relative to other oncogenic alterations in EC to identify genomic characteristics of KRAS-mut tumors that could lead to novel therapeutic options. A molecular database of 7870 ECs was queried for presence of oncogenic mutations and immunotherapy biomarkers. Comparisons were performed using Fisher-Exact/ChiSquare (p -values) and adjusted for multiple tests by Benjamini-Hochberg (q) and pairwise nonparametric analysis using Wilcoxon Method. KRAS- mut is a relatively frequent genotype in EC, detected in 16% of cases. Codon 12 was most frequently mutated, with G12D (31%) and G12V (27%) the most common subtypes. Biomarkers of immunotherapy response co-occur with KRAS- mut. Microsatellite instability-high and tumor mutational burden-high status were observed in 34.1% and 36.5% in KRAS- mut compared to 19.8% and 16.9% in KRAS- WT, respectively (p < 0.05). PD-L1 >1% was detected in 8.4% vs 6.4% of KRAS-mut vs KRAS-WT (p < 0.05). BRCA1/2 mutations were detected with similar low frequency (5.9% vs 4.9%) among KRAS- mut and KRAS- WT ECs (p > 0.05). KRAS-mut was inversely associated with Her-2 overexpression (1.8% KRAS-mut vs 13% KRAS-WT. (p < 0.001). KRAS- mut represents a genotypically distinct group of ECs. Overlap exists with genomic predictors (TMB-high, MSI-high) of immunotherapy response, suggesting a possible biomarker-driven combination option with immunotherapy. Clinical trials to evaluate these strategies should be developed. • KRAS- mutated tumors represent a genotypically distinct group of ECs and occur in 16% of cases. • KRAS -mutated ECs are associated with longer overall mean survival compared to KRAS-WT ECs. • Overlaps with predictors of immunotherapy response suggest a possible biomarker-driven combination option. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00908258
Volume :
191
Database :
Academic Search Index
Journal :
Gynecologic Oncology
Publication Type :
Academic Journal
Accession number :
181540994
Full Text :
https://doi.org/10.1016/j.ygyno.2024.10.026