Prevalence of homologous recombination deficiency in different molecular subgroups of endometrial carcinomas.

e17631 Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) has been studied to show positive efficacy in endometrial cancer (EC). However, rational candidates for precision treatment with PARPi need to be further explored. Recently, it has been reported that tumors with homologous recombination deficiency (HRD) are sensitive to PARPi. Here, we aimed to assess the relationship between HRD and molecular subgroups in EC. Methods: HRD statues and gene characteristics of 372 EC patients were retrospectively collected from August, 2022 to August, 2024. HRD score was calculated as the sum of loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transitions (LST) scores based on the next-generation sequencing (NGS) data. Results: Of the EC that underwent NGS testing, there were 5.38% (20/372) patients with BRCA1/2 mutations, and the top two BRCA1/2 mutated subgroups were microsatellite instability-high (MSI-H) (2.96%) and copy number low (CN-L) (1.88%) subgroups. However, there were 10.75% (40/372) patients with positive HRD, which is largely restricted to copy number high (CN-H) (4.57%), CN-L (2.96%) and MSI-H (2.96%) subgroup. Interestingly, based on HRD score with the cutoff of 30, there were mostly CN-H and CN-L subgroups and almost no POLE mutation and MSI-H subgroups in non BRCA1/2 mutation and positive HRD patients. Conclusions: BRCA1/2 mutations and positive HRD were seen in 5.38% and 10.75% EC patients, respectively. HRD score testing, based on LOH, TAI, and LST, may help select patients benefiting from PARPi with particular reference to CN-H and CN-L subgroups. Prevalence of HRD statues in different molecular subgroups of EC. HRD Non-HRD Molecular Subgroups All BRCA1/2 mutation HRD score≥30 POLE mut 1(0.27%) 1(0.27%) 0(0%) 8(2.15%) MSI-H 11(2.96%) 11(2.96%) 0(0%) 64(17.20%) CN-H 17(4.57%) 1(0.27%) 16(4.30%) 64(17.20%) CN-L 11(2.96%) 7(1.88%) 4(1.08%) 196(52.69%) HRD: Homologous recombination deficiency; EC: endometrial carcinomas; POLE mut: POLE mutations; MSI-H: microsatellite instability-high; CN-L: copy number low; CN-H: copy number high.