POLE mutation

Our results indicate that integrated morpho-molecular FIGO 2023 staging significantly impacts both stage and risk group stratification, and will benefit EC patients, particularly in high-grade early stage ECs, with potential treatment implications. Further comprehensive studies are needed to fully establish the implications of molecular classification in the FIGO 2023 staging system.

Endometrial carcinomas with SB-GN represent a distinct and aggressive tumor group characterized by solid growth pattern, prominent necrosis, frequent basaloid morphology, high rates of CTNNB1 mutations, and aberrant β-catenin staining. Our results demonstrate that endometrial carcinomas with SB-GN and PiMHECs share similar clinicopathologic and molecular profiles, supporting a unified biological spectrum.

However, omitting peritoneal cytology from prognostic assessment may risk undertreatment. Continued refinement in quantifying lympho-vascular space invasion (LVSI) and differentiating complex endometrial-myometrial junctions from genuine myometrial invasion remains a challenge.

Comprehensive genomic profiling assay was informative, allowing for correlation of MLH1 methylation and POLE genotype results with tumor mutation burden and mutational signature. Taken together, our data highlight the need for integrated approach in endometrial carcinoma biomarker testing, integrating NGS and MLH1 promoter methylation status, the latter of which benefits from assessing both regions C and D. Finding of MLH1 promoter methylation does not rule out either Lynch syndrome or ultramutated (POLE) carcinoma.

It also includes a concise summary of functional significance for each variant. PolED aims to assist in clinical decision-making, guide personalized therapy, and promote further research.

Given the ethnic origin of the Martinique population, these data suggest that CCNE1 amplification may be linked to African genetic heritage and could explain the over-incidence of non-endometrioid subtypes in these populations. Furthermore, our study contributes to addressing racial disparities in endometrial cancer outcomes by providing crucial insights into the genetic factors that may influence the prognosis of African-descended populations.

Identifying the subset of POLE mutations that cause LOP is critical to distinguish patients likely to respond to immunotherapy. Patients with CRC with LOP POLE mutant tumors experienced deep, sustained response to immunotherapy but were resistant to standard cytotoxic chemotherapy, in stark contrast to those with non-LOP POLE mutations.

The DFS of the p53abn subtype in CCOC was calculated (HR = 5.52, 95% CI: 3.43-8.90, p = 0.000). The TCGA subtypes of EC may exhibit similarities in prognosis between ENOC and CCOC.

Our findings reveal that EC is characterized by widespread miRNA deregulation, with a unique global down-regulation signature in POLE-mutated tumors. These results highlight the potential of miRNAs as complementary biomarkers for classification and potential targets in EC.

P1/2, N=20, Active, not recruiting, City of Hope Medical Center | Trial completion date: Oct 2025 --> Jun 2026 | Trial primary completion date: Oct 2025 --> Jun 2026

Most patients undergoing MPA therapy were classified as having NSMP. Genetic alterations, specifically mutations in PTEN and PIK3CA, were significantly associated with treatment outcomes, highlighting their potential as prognostic biomarkers.

As for dMMR subgroups (MLH1 me+, Lynch and Lynch-like), KEAP1 and FBXW7 mutations, which may have potential predictive effect of immunotherapy, were enriched in the Lynch subgroup. dMMR ECs has distinctive genomic profile with molecular heterogeneity, which may have potential prognostic and therapeutic implications.