TY - JOUR
T1 - Prognostic refinement of NSMP high-risk endometrial cancers using oestrogen receptor immunohistochemistry
AU - Vermij, Lisa
AU - Jobsen, Jan J
AU - León-Castillo, Alicia
AU - Brinkhuis, Mariel
AU - Roothaan, Suzan
AU - Powell, Melanie E
AU - de Boer, Stephanie M
AU - Khaw, Pearly
AU - Mileshkin, Linda R
AU - Fyles, Anthony
AU - Leary, Alexandra
AU - Genestie, Catherine
AU - Jürgenliemk-Schulz, Ina M
AU - Crosbie, Emma J
AU - Mackay, Helen J
AU - Nijman, Hans W
AU - Nout, Remi A
AU - Smit, Vincent T H B M
AU - Creutzberg, Carien L
AU - Horeweg, Nanda
AU - Bosse, Tjalling
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/3/30
Y1 - 2023/3/30
N2 - 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.
AB - 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.
KW - Biomarkers, Tumor/genetics
KW - Endometrial Neoplasms/pathology
KW - Female
KW - Humans
KW - Immunohistochemistry
KW - Neural Cell Adhesion Molecule L1/metabolism
KW - Prognosis
KW - Prospective Studies
KW - Receptors, Estrogen
UR - http://www.scopus.com/inward/record.url?scp=85146795657&partnerID=8YFLogxK
U2 - 10.1038/s41416-023-02141-0
DO - 10.1038/s41416-023-02141-0
M3 - Article
C2 - 36690721
SN - 0007-0920
VL - 128
SP - 1360
EP - 1368
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 7
ER -