A Pilot study of POLE mutations in endometrial cancer and its
clinicopathological correlation with Microsatellite Instability and P53
mutations
Abstract
Objective To determine the prevalence of Polymerase Epsilon gene (POLE)
mutation, P53 mutations, and mismatch repair deficiency(dMMR) in
endometrial cancer, followed by clinicopathological correlation and
survival analysis Design- retrospective cohort tested prospectively and
analysed for survival functions based on the findings Setting- Single
institution, tertiary care centre Sample- Blocks of 48 consecutive
patients with primary endometrial carcinoma were subjected to the
molecular profiling Methods- Molecular classification of endometrial
cancer by POLE ultramutated ,dMMR using IHC (MLH1, MH2, MSH6), and Copy
number high/low (p53on IHC) was done on the preserved paraffin blocks
Main Outcome Measures- prevalence of POLE mutation, P53 mutations, and
deficient MMR in endometrial cancer, followed by clinicopathological
correlation and survival analysis Results Eleven (22.9%) patients were
dMMR , 3 ( 6.3%) had POLE mutation, while 2 (4.1%) had both POLE and
P53 mutations (regarded as multiple classifiers). Twelve (25.0%)
patients were found to have P53 mutations, while the remaining 20
(41.7%) had no specific molecular profile (NSMP). Median follow up
duration was 43.5 (2-62) months with 8 recurrences and 9 deaths. Tumors
with POLE mutation had the most favourable prognosis followed by the
NSMP and the MMR mutated group while the P53 and multiple classifier
groups had the worst prognosis in terms of OS ( Log rank p : 0.006) and
PFS ( Log rank p : 0.001). Conclusion Integrated approach of molecular
profiling should be expanded to routine testing in endometrial cancers
to streamline treatment options and utilize targeted therapy such as
immunotherapy Funding Institutional internal funding