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Peer-reviewedCC BY 4.0Cancers

Integrated Molecular Classification of Endometrial Cancer: Impact on Diagnosis, Prognosis, and Clinical Management—A Systematic Review

  • Silvio Antonio Galeano Reyes1,2,3
  • María Eugenia Fraile Bethencourt1,2,3
  • Serena Lacerenza1,2,3
  • Carmen Camacho García1,2,3
  • José Ernesto Moro Rodríguez4
  • Pablo Bueno Ortiz1,2,3
  • Víctor Macarrón Aguilera1,2,3
  • Ivan Domazetovski1,2,3
  • Miguel Andújar Sánchez1,2,3
4 affiliations
  1. 1Department of Pathological Anatomy, Complejo Hospitalario Universitario Insular-Materno Infantil de Gran Canaria, 35016 Las palmas de Gran Canaria, Spain
  2. 2Fundación Instituto de Investigación Sanitaria de Canarias (FIISC), 35012 Las palmas de Gran Canaria, Spain
  3. 3Instituto de Investigación Sanitaria de Canarias (IISC), 35019 Las Palmas de Gran Canaria, Spain
  4. 4Pathological Anatomy Area, Universidad Rey Juan Carlos, 28922 Madrid, Spain
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Abstract

Objective: To systematically review the literature on the impact of integrated molecular classification of endometrial cancer on diagnosis, prognostic stratification, and clinical management. Methods: A systematic search was conducted in PubMed/MEDLINE, Web of Science, Scopus, and Cochrane Library (January 2013–December 2025), following PRISMA 2020 guidelines. We included original studies, systematic reviews, clinical guidelines, and cost-effectiveness analyses applying TCGA molecular classification or its surrogate classifiers (ProMisE, TransPORTEC). Data were extracted on subtype distribution, survival outcomes, hazard ratios, stage migration, and therapeutic implications. Results: Fifty studies were included. Of these, 13 provided data on molecular subtype distribution (comprising 3527 patients), 8 reported survival outcomes, and 7 reported hazard ratios. The weighted subtype distribution from the 13 studies was as follows: POLEmut 8.9%, MMRd 25.8%, p53abn 16.7%, and NSMP 48.2%. POLEmut was associated with an excellent prognosis (5-year overall survival >95%, hazard ratio <0.5), while p53abn represented the poorest prognosis group (5-year disease-free survival 33–58%, hazard ratio >2.0). p53abn was the only independent risk factor for peritoneal (odds ratio 8.54) and vaginal (odds ratio 6.51) recurrence. Molecular classification modified risk group assignment in 6–33% of patients and improved prognostic discrimination of the 2023 FIGO staging system. Therapeutic implications include treatment de-escalation in POLEmut, immunotherapy in MMRd, and intensive chemotherapy in p53abn. Barriers to implementation include access to POLE sequencing and cost-effectiveness. Conclusions: Integrated molecular classification is an essential tool for prognostic stratification and treatment personalization in endometrial cancer. Molecular subtypes demonstrate clearly differentiated prognostic profiles and recurrence patterns, justifying their systematic incorporation into clinical practice and international guidelines.

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Cite

BibTeXRIS
BibTeX
@article{reyes2026integrated,
  title = {{Integrated Molecular Classification of Endometrial Cancer: Impact on Diagnosis, Prognosis, and Clinical Management—A Systematic Review}},
  author = {Silvio Antonio Galeano Reyes and María Eugenia Fraile Bethencourt and Serena Lacerenza and Carmen Camacho García and José Ernesto Moro Rodríguez and Pablo Bueno Ortiz and Víctor Macarrón Aguilera and Ivan Domazetovski and Miguel Andújar Sánchez},
  journal = {Cancers},
  year = {2026},
  month = oct,
  doi = {10.3390/cancers18203316},
  url = {https://www.mdpi.com/2072-6694/18/20/3316},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Integrated Molecular Classification of Endometrial Cancer: Impact on Diagnosis, Prognosis, and Clinical Management—A Systematic Review
AU  - Silvio Antonio Galeano Reyes
AU  - María Eugenia Fraile Bethencourt
AU  - Serena Lacerenza
AU  - Carmen Camacho García
AU  - José Ernesto Moro Rodríguez
AU  - Pablo Bueno Ortiz
AU  - Víctor Macarrón Aguilera
AU  - Ivan Domazetovski
AU  - Miguel Andújar Sánchez
PY  - 2026
DA  - 2026/10/01
JO  - Cancers
DO  - 10.3390/cancers18203316
UR  - https://www.mdpi.com/2072-6694/18/20/3316
AB  - Objective: To systematically review the literature on the impact of integrated molecular classification of endometrial cancer on diagnosis, prognostic stratification, and clinical management. Methods: A systematic search was conducted in PubMed/MEDLINE, Web of Science, Scopus, and Cochrane Library (January 2013–December 2025), following PRISMA 2020 guidelines. We included original studies, systematic reviews, clinical guidelines, and cost-effectiveness analyses applying TCGA molecular classification or its surrogate classifiers (ProMisE, TransPORTEC). Data were extracted on subtype distribution, survival outcomes, hazard ratios, stage migration, and therapeutic implications. Results: Fifty studies were included. Of these, 13 provided data on molecular subtype distribution (comprising 3527 patients), 8 reported survival outcomes, and 7 reported hazard ratios. The weighted subtype distribution from the 13 studies was as follows: POLEmut 8.9%, MMRd 25.8%, p53abn 16.7%, and NSMP 48.2%. POLEmut was associated with an excellent prognosis (5-year overall survival >95%, hazard ratio <0.5), while p53abn represented the poorest prognosis group (5-year disease-free survival 33–58%, hazard ratio >2.0). p53abn was the only independent risk factor for peritoneal (odds ratio 8.54) and vaginal (odds ratio 6.51) recurrence. Molecular classification modified risk group assignment in 6–33% of patients and improved prognostic discrimination of the 2023 FIGO staging system. Therapeutic implications include treatment de-escalation in POLEmut, immunotherapy in MMRd, and intensive chemotherapy in p53abn. Barriers to implementation include access to POLE sequencing and cost-effectiveness. Conclusions: Integrated molecular classification is an essential tool for prognostic stratification and treatment personalization in endometrial cancer. Molecular subtypes demonstrate clearly differentiated prognostic profiles and recurrence patterns, justifying their systematic incorporation into clinical practice and international guidelines.
SN  - 2072-6694
ER  -