Prognostic Refinement of NSMP High-risk Endometrial Cancers Using Oestrogen Receptor Immunohistochemistry

Overview

Journal Br J Cancer

Specialty Oncology

Date 2023 Jan 23

PMID 36690721

Authors

Lisa Vermij

Jan J Jobsen

Alicia Leon-Castillo

Mariel Brinkhuis

Suzan Roothaan

Melanie E Powell

Stephanie M de Boer

Pearly Khaw

Linda R Mileshkin

Anthony Fyles

Alexandra Leary

Catherine Genestie

Ina M Jurgenliemk-Schulz

Emma J Crosbie

Helen J MacKay

Hans W Nijman

Remi A Nout

Vincent T H B M Smit

Carien L Creutzberg

Nanda Horeweg

Tjalling Bosse

Affiliations

Soon will be listed here.

Abstract

Background: Risk-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.

Methods: Paraffin-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.

Results: In total, 648 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).

Conclusions: We confirmed the prognostic impact of the molecular classification, age, stage, and adjuvant CTRT in a large cohort of high-risk EC. ER-positivity is a strong favourable prognostic factor in NSMP HR-EC and identifies a homogeneous subgroup of NSMP tumours. Assessment of ER status in high-risk NSMP EC is feasible in clinical practice and could improve risk stratification and treatment.

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References

Siegel R, Miller K, Fuchs H, Jemal A . Cancer statistics, 2022. CA Cancer J Clin. 2022; 72(1):7-33. DOI: 10.3322/caac.21708. View

Creutzberg C, van Putten W, Warlam-Rodenhuis C, van den Bergh A, De Winter K, Koper P . Outcome of high-risk stage IC, grade 3, compared with stage I endometrial carcinoma patients: the Postoperative Radiation Therapy in Endometrial Carcinoma Trial. J Clin Oncol. 2004; 22(7):1234-41. DOI: 10.1200/JCO.2004.08.159. View

Straughn J, Huh W, Orr Jr J, Kelly F, Roland P, Gold M . Stage IC adenocarcinoma of the endometrium: survival comparisons of surgically staged patients with and without adjuvant radiation therapy. Gynecol Oncol. 2003; 89(2):295-300. DOI: 10.1016/s0090-8258(03)00087-8. View

Bosse T, Peters E, Creutzberg C, Jurgenliemk-Schulz I, Jobsen J, Mens J . Substantial lymph-vascular space invasion (LVSI) is a significant risk factor for recurrence in endometrial cancer--A pooled analysis of PORTEC 1 and 2 trials. Eur J Cancer. 2015; 51(13):1742-50. DOI: 10.1016/j.ejca.2015.05.015. View

Colombo N, Creutzberg C, Amant F, Bosse T, Gonzalez-Martin A, Ledermann J . ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: diagnosis, treatment and follow-up. Ann Oncol. 2015; 27(1):16-41. DOI: 10.1093/annonc/mdv484. View

de Boer S, Powell M, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C . Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2018; 19(3):295-309. PMC: 5840256. DOI: 10.1016/S1470-2045(18)30079-2. View

de Boer S, Powell M, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C . Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial. Lancet Oncol. 2019; 20(9):1273-1285. PMC: 6722042. DOI: 10.1016/S1470-2045(19)30395-X. View

de Boer S, Wortman B, Bosse T, Powell M, Singh N, Hollema H . Clinical consequences of upfront pathology review in the randomised PORTEC-3 trial for high-risk endometrial cancer. Ann Oncol. 2017; 29(2):424-430. PMC: 5834053. DOI: 10.1093/annonc/mdx753. View

Stelloo E, Bosse T, Nout R, MacKay H, Church D, Nijman H . Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative. Mod Pathol. 2015; 28(6):836-44. DOI: 10.1038/modpathol.2015.43. View

10.

Stelloo E, Nout R, Osse E, Jurgenliemk-Schulz I, Jobsen J, Lutgens L . Improved Risk Assessment by Integrating Molecular and Clinicopathological Factors in Early-stage Endometrial Cancer-Combined Analysis of the PORTEC Cohorts. Clin Cancer Res. 2016; 22(16):4215-24. DOI: 10.1158/1078-0432.CCR-15-2878. View

11.

Bosse T, Nout R, McAlpine J, McConechy M, Britton H, Hussein Y . Molecular Classification of Grade 3 Endometrioid Endometrial Cancers Identifies Distinct Prognostic Subgroups. Am J Surg Pathol. 2018; 42(5):561-568. PMC: 5893364. DOI: 10.1097/PAS.0000000000001020. View

12.

Leon-Castillo A, de Boer S, Powell M, Mileshkin L, MacKay H, Leary A . Molecular Classification of the PORTEC-3 Trial for High-Risk Endometrial Cancer: Impact on Prognosis and Benefit From Adjuvant Therapy. J Clin Oncol. 2020; 38(29):3388-3397. PMC: 7527156. DOI: 10.1200/JCO.20.00549. View

13.

Leon-Castillo A, Horeweg N, Peters E, Rutten T, Ter Haar N, Smit V . Prognostic relevance of the molecular classification in high-grade endometrial cancer for patients staged by lymphadenectomy and without adjuvant treatment. Gynecol Oncol. 2022; 164(3):577-586. DOI: 10.1016/j.ygyno.2022.01.007. View

14.

Talhouk A, McConechy M, Leung S, Li-Chang H, Kwon J, Melnyk N . A clinically applicable molecular-based classification for endometrial cancers. Br J Cancer. 2015; 113(2):299-310. PMC: 4506381. DOI: 10.1038/bjc.2015.190. View

15.

Talhouk A, McConechy M, Leung S, Yang W, Lum A, Senz J . Confirmation of ProMisE: A simple, genomics-based clinical classifier for endometrial cancer. Cancer. 2017; 123(5):802-813. DOI: 10.1002/cncr.30496. View

16.

Kommoss S, McConechy M, Leung S, Bunz A, Magrill J, Britton H . Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series. Ann Oncol. 2018; 29(5):1180-1188. DOI: 10.1093/annonc/mdy058. View

17.

Concin N, Matias-Guiu X, Vergote I, Cibula D, Mirza M, Marnitz S . ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Int J Gynecol Cancer. 2021; 31(1):12-39. DOI: 10.1136/ijgc-2020-002230. View

19.

Kurnit K, Kim G, Fellman B, Urbauer D, Mills G, Zhang W . CTNNB1 (beta-catenin) mutation identifies low grade, early stage endometrial cancer patients at increased risk of recurrence. Mod Pathol. 2017; 30(7):1032-1041. PMC: 5493522. DOI: 10.1038/modpathol.2017.15. View

20.

Costigan D, Dong F, Nucci M, Howitt B . Clinicopathologic and Immunohistochemical Correlates of CTNNB1 Mutated Endometrial Endometrioid Carcinoma. Int J Gynecol Pathol. 2019; 39(2):119-127. DOI: 10.1097/PGP.0000000000000583. View

21.

Bosse T, Nout R, Stelloo E, Dreef E, Nijman H, Jurgenliemk-Schulz I . L1 cell adhesion molecule is a strong predictor for distant recurrence and overall survival in early stage endometrial cancer: pooled PORTEC trial results. Eur J Cancer. 2014; 50(15):2602-10. DOI: 10.1016/j.ejca.2014.07.014. View