Prognostic relevance of the molecular classification in high-grade endometrial cancer for patients staged by lymphadenectomy and without adjuvant treatment

Alicia Leon-Castillo; Nanda Horeweg; Elke E M Peters; Tessa Rutten; Natalja Ter Haar; Vincent T H B M Smit; Cor D Kroon; Marie Boennelycke; Estrid Hogdall; Claus Hogdall; Remi R A Nout; Carien L Creutzberg; Gitte Ortoft; Tjalling Bosse

doi:10.1016/j.ygyno.2022.01.007

Prognostic relevance of the molecular classification in high-grade endometrial cancer for patients staged by lymphadenectomy and without adjuvant treatment

Gynecol Oncol. 2022 Mar;164(3):577-586. doi: 10.1016/j.ygyno.2022.01.007. Epub 2022 Jan 23.

Authors

Affiliations

¹ Leiden University Medical Center, Department of Pathology, P.O. Box 9600, 2300, RC, Leiden, the Netherlands. Electronic address: [email protected].
² Leiden University Medical Center, Department of Radiation Oncology, P.O. Box 9600, 2300, RC, Leiden, the Netherlands. Electronic address: [email protected].
³ Leiden University Medical Center, Department of Pathology, P.O. Box 9600, 2300, RC, Leiden, the Netherlands; Haaglanden Medical Center, P.O. Box 432, 2501, CK, The Hague, the Netherlands. Electronic address: [email protected].
⁴ Leiden University Medical Center, Department of Pathology, P.O. Box 9600, 2300, RC, Leiden, the Netherlands. Electronic address: [email protected].
⁵ Leiden University Medical Center, Department of Pathology, P.O. Box 9600, 2300, RC, Leiden, the Netherlands. Electronic address: [email protected].
⁶ Leiden University Medical Center, Department of Pathology, P.O. Box 9600, 2300, RC, Leiden, the Netherlands. Electronic address: [email protected].
⁷ Leiden University Medical Center, Department of Gynaecology, P.O. Box 9600, 2300, RC, Leiden, the Netherlands. Electronic address: [email protected].
⁸ Department of Pathology, Copenhagen University Hospital, Herlev and Gentofte Hospital, Borgmester Ib Juuls Vej 73, 2730 Herlev, Denmark. Electronic address: [email protected].
⁹ Department of Pathology, Copenhagen University Hospital, Herlev and Gentofte Hospital, Borgmester Ib Juuls Vej 73, 2730 Herlev, Denmark. Electronic address: [email protected].
¹⁰ Copenhagen University Hospital, Rigshospitalet, Department of Gynaecology, Juliane Maries Vej 8, 2100 Copenhagen, OE, Denmark. Electronic address: [email protected].
¹¹ Leiden University Medical Center, Department of Radiation Oncology, P.O. Box 9600, 2300, RC, Leiden, the Netherlands. Electronic address: [email protected].
¹² Leiden University Medical Center, Department of Radiation Oncology, P.O. Box 9600, 2300, RC, Leiden, the Netherlands. Electronic address: [email protected].
¹³ Copenhagen University Hospital, Rigshospitalet, Department of Gynaecology, Juliane Maries Vej 8, 2100 Copenhagen, OE, Denmark. Electronic address: [email protected].
¹⁴ Leiden University Medical Center, Department of Pathology, P.O. Box 9600, 2300, RC, Leiden, the Netherlands. Electronic address: [email protected].

PMID: 35078648
DOI: 10.1016/j.ygyno.2022.01.007

Abstract

Introduction: The clinical role of the molecular endometrial cancer (EC) classification has not been fully explored in patients staged with lymphadenectomy or without adjuvant treatment, conditions that could potentially moderate the prognostic value of the classification. We aimed to evaluate the clinical outcome of the molecular subgroups in patients with high-grade EC staged by lymphadenectomy and those without adjuvant treatment.

Methods: DNA-sequencing for the detection of pathogenic POLE-exonuclease domain mutations and immunohistochemistry for mismatch repair (MMR) proteins and p53 expression were performed on 412 high-grade EC from the Danish Gynaecological Cancer Database (2005-2012) to classify them as POLE-ultramutated (POLEmut), MMR-deficient (MMRd), p53-mutant (p53abn), or no specific molecular profile (NSMP). Patients with stage IV or residual disease after surgery were excluded. Kaplan-Meier method, log-rank test and Cox proportional hazard models were used for analysis.

Results: Molecular analysis was successful in 367 EC; 251 patients had undergone lymphadenectomy. Five-year recurrence rates in this subgroup of patients was 36.7% for women with p53abn EC, 0.0% for POLEmut EC, 13.4% for MMRd EC and 42.9% for NSMP EC (p < 0.001). Similar results were observed among stage IA-IB patients. Among patients without adjuvant treatment (n = 264), none with POLEmut EC (n = 26) had a recurrence.

Conclusion: The molecular EC classification has strong prognostic value, independent of clinicopathological factors, also among high-grade EC patients staged by lymphadenectomy and those without adjuvant treatment. The unfavourable prognosis of early-stage p53abn EC is not due to undetected lymph node metastasis, and the indolent behaviour of POLEmut EC is independent of adjuvant treatment.

Keywords: Endometrial cancer; Lymphadenectomy; Lymphovascular space invasion; Molecular risk factors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor / genetics
Endometrial Neoplasms* / genetics
Endometrial Neoplasms* / metabolism
Endometrial Neoplasms* / surgery
Female
Humans
Lymph Node Excision
Mutation
Prognosis
Tumor Suppressor Protein p53* / genetics

Substances

Biomarkers, Tumor
Tumor Suppressor Protein p53