POLE mutation

We highlight the utility of a liquid biopsy approach to aid selection of GI cancer patients harbouring rare POLE mutations for immunotherapy, leading to complete metabolic response in addition to radiologic responses and extended survival in all three patients. This study advocates for specialised multi-disciplinary teams performing shared clinical decision making to advance personalised care and improve outcomes of a subset of GI cancer patients with a poor prognosis.

This review evaluates the evidence supporting de-escalated therapy in carefully selected patients with POLE mutated endometrial carcinoma. We highlight the critical considerations to make effective and safe treatment decisions for patients with these tumors.

The study's findings diverge from prognostic implications of TCGA-surrogate molecular types, suggesting genetic diversity and ethnicity as potential outcome determinants in South Indian endometrial cancer patients.

POLE mutations in endometrial cancer are associated with a favorable prognosis and show promising potential for immunotherapy. Molecular subtyping that incorporates POLE mutation status should be considered standard practice for risk stratification and treatment planning.

In conclusion, the different prognosis of ER-positive vs ER-negative NSMP endometrial carcinoma is not attributable to ER status itself, but rather to its strong correlation with histotype and other clinicopathological risk factors. Limited specificity of GATA3, TTF1 and KRAS warrant caution in their use as diagnostic markers of mesonephric-like carcinoma.

However, still little is known about the immune dysregulation that occurs during the precancerous stage and its impact on subsequent malignant progression. This review systematically describes the changes in the immune microenvironment during the process from normal endometrium to endometrial cancer, emphasizing that endometrial intraepithelial neoplasia is a key stage of immune imbalance, thus paving the way for early immune intervention and precise immunotherapy.

This commentary underscores the need for functional assays and validation through multi-center studies to establish the pathogenicity and clinical relevance of non-EDMs. Furthermore, it advocates for the incorporation of comprehensive POLE sequencing, including non-EDM regions, into standard molecular subtyping frameworks for CRC to refine personalized treatment strategies.

Molecular sub-types in endometrial cancer reflect distinct and reproducible phenotypes. However, classic histopathologic features remain the strongest predictors of nodal spread and SLN detection failure.

Three KRAS-mutated tumors also had at least focal mesonephric-like histology. Although rare, p53 wild-type tumors represent a small subset of OCS that show distinct clinical and histologic features and are largely driven by KRAS mutations.

AlphaTMB improves survival prediction beyond TMB alone, better captures immunogenic tumor profiles, and reflects more accurate patient stratification. This AI derived somatic mutations pathogenicity scoring represents a step toward personalized immuno-oncology and merits further validation in prospective studies.

P2, N=62, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2026 --> Feb 2027

MMR and p53 IHC serve as practical frontline tools, while POLE sequencing should be prioritized for intermediate- and high-risk endometrioid tumors. Expanded molecular testing in Asian populations is essential to refine risk stratification and optimize individualized management.