POLE mutation

For early-stage POLE-mutated CRC with favorable prognosis, off-label adjuvant immunotherapy may bring unnecessary toxicity risks. It is necessary to conduct rigorous patient selection, comprehensive risk-benefit evaluation, and close monitoring of organ function during treatment, so as to provide reference for the standardized clinical application of ICIs in this population.

P4, N=80, Not yet recruiting, Hospital Universitari de Bellvitge | Trial completion date: Sep 2028 --> Jan 2035 | Initiation date: Sep 2026 --> Jan 2027 | Trial primary completion date: May 2027 --> Apr 2031

Minimal microsatellite shift is commonly detected in MSI-H cases, and some cases are difficult to interpret due to their classification within the equivocal range. Increasing the number of microsatellite loci, combined with visualization graph comparison and integration of mismatch repair protein immunophenotype and histological features, can effectively improve the accuracy of MSI-H interpretation.

Molecular classification provides clinically meaningful information beyond traditional histopathologic factors and is closely associated with the risk of lymph-node metastasis in endometrial cancer. The consistently low nodal involvement observed in POLEmut and the high risk observed in p53abn support a more tailored approach to surgical staging.

This case underscores the role of immunotherapy in POLE-mutated tumors regardless of the site of origin and highlights the potential usefulness of molecular profiling in rare malignancies. In line with the agnostic approach used for microsatellite instability, molecular-driven clinical trials should be prioritized over histology-based studies to optimize treatment strategies for these orphan diseases.

The complete response to levonorgestrel intra-uterine device therapy was lower than expected for endometrial intra-epithelial neoplasia. Response rates varied by molecular classification, with worse outcomes observed in deficient mismatch repair and p53 abnormal sub-types. Although limited by sample size, these findings suggest that levonorgestrel intra-uterine device therapy may not be sufficient for all molecular sub-groups.

P1, N=115, Recruiting, Jecho Biopharmaceuticals Co., Ltd.

In stage I-II EC, focal LVSI does not worsen oncologic outcomes across molecular subgroups. In contrast, substantial LVSI associates with aggressive clinicopathologic features and independently predicts poorer disease-free survival in selected molecular groups, increasing recurrence risk by approximately 2.5-2.8-fold.

Molecular classification is strongly associated with nodal involvement and survival outcomes in early-stage endometrial cancer. Integrating molecular subtype with clinicopathologic factors may improve recurrence risk stratification and guide individualized surgical and adjuvant treatment strategies.

Detected variants were recurrent hotspot mutations. The study underscores the importance of integrating POLE testing into routine diagnostic workflows for endometrial carcinoma in India.

Current evidence suggests that PESCC may exhibit molecular and immunophenotypic features that differ from conventional endometrial adenocarcinoma; however, available data remain sparse. Further accumulation of molecularly characterized cases is necessary to clarify its biological behavior and staging implications.