Beyond Molecular Classification: The Incremental Value of Prognostic Biomarkers in Endometrial Cancer
5 affiliations
- 1Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania
- 2Department of Obstetrics and Gynecology, Cuza Voda Hospital, 700038 Iasi, Romania
- 3Department of Obstetrics and Gynecology, “Carol Davila” University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd., 050474 Bucharest, Romania
- 4Department of Obstetrics and Gynecology, Elias University Emergency Hospital, 17 Mărăști Blvd., 011461 Bucharest, Romania
- 5Department of Obstetrics, Gynecology and Human Reproduction, “Nicolae Testemițanu” State University of Medicine and Pharmacy, MD-2004 Chișinău, Moldova
Abstract
Molecular classification underpins prognostic assessment in endometrial carcinoma, but heterogeneity persists within molecular classes. This narrative review examines whether tissue-based, circulating and emerging biomarkers add prognostic information beyond molecular class and clinicopathological factors. We distinguish four evidentiary levels: prognostic association, independence after adjustment for molecular class, within-class stratification and incremental predictive performance. Clinical utility is considered separately. Estrogen receptor (ER) status now contributes to risk stratification of no specific molecular profile (NSMP) tumors in the 2025 European guidelines, primarily on within-class prognostic evidence. Its incremental predictive performance has been demonstrated only in high-risk disease, with internal validation. Clinical utility remains unproven, and findings within mismatch repair-deficient disease are discordant. CTNNB1 mutation has shown inconsistent associations with recurrence, mainly in early-stage disease. Chromosome 1q32.1 amplification was associated with recurrence within NSMP in two cohorts. Neither marker has been formally assessed for incremental predictive performance. Where model comparisons were performed, gains in discrimination were generally modest. Larger gains arose from small samples or models without external validation, and external validation remained uncommon. No individual biomarker examined has demonstrated prospective clinical utility on its own.
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BibTeX
@article{tirnovanu2026beyond,
title = {{Beyond Molecular Classification: The Incremental Value of Prognostic Biomarkers in Endometrial Cancer}},
author = {Vlad Gabriel Tirnovanu and Iustina Petra Solomon Condriuc and Raluca Anamaria Mogos and Daniela Roxana Matasariu and Alexandru Filipescu and Mihaela Burac and Mihaela Camelia Tirnovanu and Demetra Socolov and Alexandru Carauleanu},
journal = {Journal of Clinical Medicine},
year = {2026},
month = oct,
doi = {10.3390/jcm15208154},
url = {https://www.mdpi.com/2077-0383/15/20/8154},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Beyond Molecular Classification: The Incremental Value of Prognostic Biomarkers in Endometrial Cancer
AU - Vlad Gabriel Tirnovanu
AU - Iustina Petra Solomon Condriuc
AU - Raluca Anamaria Mogos
AU - Daniela Roxana Matasariu
AU - Alexandru Filipescu
AU - Mihaela Burac
AU - Mihaela Camelia Tirnovanu
AU - Demetra Socolov
AU - Alexandru Carauleanu
PY - 2026
DA - 2026/10/01
JO - Journal of Clinical Medicine
DO - 10.3390/jcm15208154
UR - https://www.mdpi.com/2077-0383/15/20/8154
AB - Molecular classification underpins prognostic assessment in endometrial carcinoma, but heterogeneity persists within molecular classes. This narrative review examines whether tissue-based, circulating and emerging biomarkers add prognostic information beyond molecular class and clinicopathological factors. We distinguish four evidentiary levels: prognostic association, independence after adjustment for molecular class, within-class stratification and incremental predictive performance. Clinical utility is considered separately. Estrogen receptor (ER) status now contributes to risk stratification of no specific molecular profile (NSMP) tumors in the 2025 European guidelines, primarily on within-class prognostic evidence. Its incremental predictive performance has been demonstrated only in high-risk disease, with internal validation. Clinical utility remains unproven, and findings within mismatch repair-deficient disease are discordant. CTNNB1 mutation has shown inconsistent associations with recurrence, mainly in early-stage disease. Chromosome 1q32.1 amplification was associated with recurrence within NSMP in two cohorts. Neither marker has been formally assessed for incremental predictive performance. Where model comparisons were performed, gains in discrimination were generally modest. Larger gains arose from small samples or models without external validation, and external validation remained uncommon. No individual biomarker examined has demonstrated prospective clinical utility on its own.
SN - 2077-0383
ER -