POLE A456P

Integrating molecular L1CAM classification can enhance risk stratification in early-stage EC, providing valuable prognostic information to guide treatment decisions and improve patient outcomes. POLE ddPCR might be a cost-effective and easy-to-perform test as an alternative to POLE NGS.

Hotspot POLE mutations can be detected using the ddPCR assay. We suggest simultaneously evaluating POLE mutation status using ddPCR and p53/mismatch repair protein expressions using immunohistochemistry, which can rapidly and accurately determine the molecular subtype of EC.

POLE-mutated ECs are typically high grade EECs in which IH, increased TILs and BN are frequently observed. Abnormal p53 expres- sion and/or loss of MMR protein expression in high grade tumours, does not exclude POLE mutations. Patients with pathogenic POLE mutations have a favourable prognosis, despite presenting advanced stage at diagnosis.

From the largest cohort of RNA-seq from endometrioid OC to date (n = 53), we identified six hypermutated samples likely driven by POLE (frequency, 11%). Our result suggests the clinical need to screen for POLE driver mutations in endometrioid OC, which can guide enrollment in immunotherapy clinical trials.

Our results realved a remarkable positive correlation between POLE mutation and TMB level in a Chinese colorectal cancer population, which suggests POLE gene will be a promising biomarker of immunotherpy for MSS colorectal tumor.