TY - JOUR
T1 - Prognostic relevance of the molecular classification in high-grade endometrial cancer for patients staged by lymphadenectomy and without adjuvant treatment
AU - Leon-Castillo, Alicia
AU - Horeweg, Nanda
AU - Peters, Elke E M
AU - Rutten, Tessa
AU - Ter Haar, Natalja
AU - Smit, Vincent T H B M
AU - Kroon, Cor D
AU - Boennelycke, Marie
AU - Hogdall, Estrid
AU - Hogdall, Claus
AU - Nout, Remi R A
AU - Creutzberg, Carien L
AU - Ortoft, Gitte
AU - Bosse, Tjalling
N1 - Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2022/3
Y1 - 2022/3
N2 - 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.
AB - 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.
KW - Biomarkers, Tumor/genetics
KW - Endometrial Neoplasms/genetics
KW - Female
KW - Humans
KW - Lymph Node Excision
KW - Mutation
KW - Prognosis
KW - Tumor Suppressor Protein p53/genetics
UR - http://www.scopus.com/inward/record.url?scp=85123263684&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2022.01.007
DO - 10.1016/j.ygyno.2022.01.007
M3 - Journal article
C2 - 35078648
SN - 0090-8258
VL - 164
SP - 577
EP - 586
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 3
ER -