Prognostic refinement of NSMP high-risk endometrial cancers using oestrogen receptor immunohistochemistry

Abstract

AbstractBackgroundRisk-assessment of endometrial cancer (EC) is based on clinicopathological factors and molecular subgroup. It is unclear whether adding hormone receptor expression, L1CAM expression or CTNNB1 status yields prognostic refinement.MethodsParaffin-embedded tumour samples of women with high-risk EC (HR-EC) from the PORTEC-3 trial (n=424), and a Dutch prospective clinical cohort called MST (n=256), were used. All cases were molecularly classified. Expression of L1CAM, ER and PR were analysed by whole-slide immunohistochemistry and CTNNB1 mutations were assessed with a next-generation sequencing. Kaplan-Meier method, log-rank tests and Cox’s proportional hazard models were used for survival analysis.ResultsIn total, 649 HR-EC were included. No independent prognostic value of ER, PR, L1CAM and CTNNB1 was found, while age, stage, and adjuvant chemotherapy had an independent impact on risk of recurrence. Subgroup-analysis showed that only in NSMP HR-EC, ER-positivity was independently associated with a reduced risk of recurrence (HR 0.33, 95%CI 0.15-0.75).ConclusionsER-positivity is a strong favourable prognostic factor in NSMP HR-EC and identifies a homogeneous subgroup of NSMP tumours. ER-positive NSMP EC may be regarded as a novel fifth molecular subgroup. Assessment of ER status in high-risk NSMP EC is feasible in clinical practice and could improve risk stratification and treatment.