Molecular Profiling of Endometrial Cancer: An Exploratory Study in Aotearoa, New Zealand

Abstract

Background: Aotearoa, New Zealand, has one of the fastest-rising rates of endometrial cancer (EC) worldwide, increasing particularly in younger Māori and Pasifika women. There is a move towards using molecular profiling to direct treatment for each EC subtype. Aim: This study aimed to explore the molecular profiling of primary EC tissue in Aotearoa. Methods: We used the PORTEC guidelines for the molecular subtyping of 90 patients’ samples into four categories: POLE-mutated, p53 abnormal, mismatch repair deficient (MMRd) and no specific molecular profile (NSMP). The CTNNB1 mutation and L1CAM expression were also included in the analysis. POLE and CTNNB1 mutations were analysed using targeted next-generation sequencing (NGS). Novel mutations were assessed using VarSome. MMRd, L1CAM and p53 abnormalities were analysed using immunohistochemistry. Results: In total, 15 samples were MMRd, 9 were p53 abnormal, 8 were POLE-mutated and the rest (56) were NSMP. Eleven samples had exon 3 CTNNB1 mutations and eleven novel POLE mutations were described. Conclusion: Surrogate markers for POLE mutations should be investigated. The validation of POLE variants and CTNNB1 mutations as part of an Aotearoa-based molecular panel is warranted.

A new strategy in molecular typing: the accuracy of an NGS panel for the molecular classification of endometrial cancers

“…Adverse effects due to excessive adjuvant chemotherapy can be avoided in patients with EC harboring POLE mutants, while patients with MMR-d EC can benefit from radiotherapy but not chemotherapy. By contrast, patients with P53-abn EC can typically benefit from chemotherapy (10,30). At present, the consensus recommendation for the molecular typing of EC is an integrated multiplatform approach using IHC and molecular detection methods to detect and classify the 4 subtypes of EC (17).…”