Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Mar;128(7):1360-1368.
doi: 10.1038/s41416-023-02141-0. Epub 2023 Jan 23.

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

Lisa Vermij  1 , Jan J Jobsen  2 , Alicia León-Castillo  1 , Mariel Brinkhuis  3 , Suzan Roothaan  3 , Melanie E Powell  4 , Stephanie M de Boer  5 , Pearly Khaw  6 , Linda R Mileshkin  7 , Anthony Fyles  8 , Alexandra Leary  9 , Catherine Genestie  10 , Ina M Jürgenliemk-Schulz  11 , Emma J Crosbie  12   13 , Helen J Mackay  14 , Hans W Nijman  15 , Remi A Nout  5 , Vincent T H B M Smit  1 , Carien L Creutzberg  5 , Nanda Horeweg  5 , Tjalling Bosse  16 ; TransPORTEC Consortium
Collaborators, Affiliations

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

Lisa Vermij et al. Br J Cancer. 2023 Mar.

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Recurrence-free survival for patients with NSMP high-risk endometrial cancer by ER and PR expression.
Kaplan–Meier survival curves of patients with NSMP high-risk endometrial cancer for recurrence-free survival by ER and PR expression.
Fig. 2
Fig. 2. Histopathological and molecular characteristics of NSMP high-risk endometrial cancers.
Histopathological and molecular landscape depicting ER and PR status, the most frequently mutated genes, histotype and grade assignment and L1CAM status of NSMP high-risk endometrial cancers (n = 161) with successful ER, PR and L1CAM immunohistochemistry and next-generation sequencing. IHC immunohistochemistry.
Fig. 3
Fig. 3. Incorporation of ER status in the molecular classification of endometrial cancer.
a Addition of a fourth step into the WHO diagnostic algorithm of the endometrial cancer (EC) molecular classification, including ER immunohistochemistry in NSMP EC. b Recurrence-free survival Kaplan–Meier curves of patients with high-risk endometrial cancer.
See this image and copyright information in PMC

References

    1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72:7–33. doi: 10.3322/caac.21708. - DOI - PubMed
    1. Creutzberg CL, van Putten WL, Warlam-Rodenhuis CC, van den Bergh AC, de Winter KA, Koper PC, et al. 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;22:1234–41. doi: 10.1200/JCO.2004.08.159. - DOI - PubMed
    1. Straughn JM, Huh WK, Orr JW, Jr., Kelly FJ, Roland PY, Gold MA, et al. Stage IC adenocarcinoma of the endometrium: survival comparisons of surgically staged patients with and without adjuvant radiation therapy. Gynecol Oncol. 2003;89:295–300. doi: 10.1016/S0090-8258(03)00087-8. - DOI - PubMed
    1. Bosse T, Peters EE, Creutzberg CL, Jurgenliemk-Schulz IM, Jobsen JJ, Mens JW, et al. 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;51:1742–50. doi: 10.1016/j.ejca.2015.05.015. - DOI - PubMed
    1. Colombo N, Creutzberg C, Amant F, Bosse T, Gonzalez-Martin A, Ledermann J, et al. ESMO-ESGO-ESTRO consensus conference on endometrial cancer: diagnosis, treatment and follow-up. Ann Oncol. 2016;27:16–41. doi: 10.1093/annonc/mdv484. - DOI - PubMed

Publication types

Substances