POLE mutation

Morphological analysis revealed that MSI-H-subtype tumors exhibited increased stromal lymphocytic infiltration; POLEmut tumors showed higher heterogeneity, solid growth patterns, and elevated tumor grade; p53abn tumors were characterized by papillary growth and serous-like features; while NSMP tumors demonstrated high stromal cellularity. This method provides an accurate and interpretable tool for molecular subtype prediction, offering a theoretical basis for future individualized treatment strategies in endometrial cancer.

Pathogenic POLE-mutant CRC constitutes a relatively rare, yet clinically important, subtype. These cancers exhibit distinct clinicopathological and genomic features. Our results indicate that mutations in the POLE gene may serve as a valuable prognostic marker and a potential indicator of benefit to immunotherapy in CRC, offering promising avenues for personalized treatment strategies.

pPOLE have been incorporated into treatment guidelines for several malignancies and are an important predictor of immunotherapy response. This study provides biological insight to guide classification and clinical management of patients with tumors harboring pPOLE.

Individualised adjuvant treatment by molecular integrated risk profile is safe and effective for patients with high-intermediate risk endometrial cancer; it spared 46% of patients with a favourable profile from adjuvant treatment, and reduces both overtreatment and undertreatment.

Using the two R-packages, we functionally confirmed both regulation of metabolism and mitochondrial activities in LOVO cells after stimulation with metformin...Machine learning using Elastic-net allowed us to build a mixed metabolism/mitochondrial activity score, which was found to be increased in the CMS1-MSI subtype and metastatic samples and to be an independent parameter predictive of BRAF-V600E mutation status in colorectal cancer. These findings underscore the pivotal role of mitochondrial metabolism in colorectal cancer subtyping and highlight its value as a predictive biomarker for personalized therapeutic strategies.

Although our cohort is small, the morphology of POLEmut ECs appears to be influenced by TMB, a phenomenon not yet described in the evolving landscape of these tumors. Taken in combination with differences in underlying genomic signatures, these findings provide an interesting springboard for better understanding POLEmut EC pathobiology.

Patients with POLE-mutated EC exhibit high SUVmax in primary tumors and also tend to show elevated uptake in non-metastatic lymph nodes.

The most frequently mutated gene is NOTCH1. Extensive fusion gene, expression and molecular cluster analyses provide a molecular portrait of this rare and enigmatic tumour type.

Integration of molecular sub-group as a stratification parameter might be considered for randomized trials in advanced/metastatic endometrial carcinoma after carboplatin-based chemotherapy. Deeper characterization of mismatch repair-proficient tumors might enhance prognostication.

Surgical stage remains a strong prognostic factor across molecular subtypes and should be considered alongside molecular classification when tailoring adjuvant treatment in EC.

The FIGO 2023 stage IA3 classification enables more precise risk stratification, particularly, in cases with low-grade tumors, estrogen receptor positivity, and favorable molecular profiles (POLE-mutated or p53 wild-type and non-specific molecular profile). However, it raises 2 critical issues: the need for appropriate staging surgery and the debate regarding the optimal grading system for ovarian endometrioid carcinoma.