Comprehensive molecular characterization of early stage grade 3 endometrioid endometrial adenocarcinoma.

Autor: Cun HT; Section of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Chicago, Chicago, USA. Electronic address: hcun@uchicago.edu., Bernard L; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, McGill University Health Centre, Montreal, Canada., Lande KT; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway., Lawson BC; Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, USA., Nesbakken AJ; Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway., Davidson B; Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Lindemann K; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Gynecologic Oncology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway., Fellman B; Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, USA., Sørlie T; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Soliman PT; Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, USA., Eriksson AGZ; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Gynecologic Oncology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway. Electronic address: aneeri@ous-hf.no.
Jazyk: angličtina
Zdroj: Gynecologic oncology [Gynecol Oncol] 2024 Oct; Vol. 189, pp. 138-145. Date of Electronic Publication: 2024 Aug 09.
DOI: 10.1016/j.ygyno.2024.07.677
Abstrakt: Objective: The treatment for stage IB grade 3 endometrioid endometrial adenocarcinoma is challenging with variable practice. Molecular characterization may help identify adjuvant therapy strategies beyond stage. We aimed to better understand the molecular features of these tumors by characterizing them by ProMisE classification, mutational signature, and commonly mutated genes.
Methods: Patients with stage IB grade 3 EEC at two institutions were included. Immunohistochemistry and whole exome sequencing were performed on archival FFPE tissue sections to determine ProMisE classification. Personal Cancer Genome Reporter was used for somatic variant annotation, and mutational signatures were generated based on COSMIC single base substitution mutational signatures.
Results: 46 patients were included with variable adjuvant treatment. Nine patients recurred (19.6%), most with extra-abdominal disease (n = 5, or 55.6%). 10 had POLE mutations (21.7%), 18 were MMR deficient (39.1%), 6 had abnormal p53 (13.0%), and 12 were p53 wildtype (26.1%). There were no recurrences in the POLE subgroup. A dominant mutational signature was identified in 38 patients: 17 SBS5 signature (44.7%), 10 SBS15 or SBS44 signature (26.3%), 7 SBS10a or SBS10b signature (18.4%), 3 SBS14 signature (7.9%), and 1 SBS40 signature (2.6%). The six patients that recurred had a SBS5 signature. Frequently mutated genes included ARID1A (n = 30, 65%), PTEN (n = 28, 61%), MUC16 (n = 27, 59%), and PIK3CA (n = 25, 54%).
Conclusions: This comprehensive evaluation found a molecularly diverse cohort of tumors, despite the same histology, stage and grade. Mutational signature SBS5 correlated with a high risk of recurrence. Further refining of endometrial cancer classification may enable more precise patient stratification and personalized treatment approaches.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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