Clinical outcomes of patients with POLE mutated endometrioid endometrial cancer.
Adult
Aged
Carcinoma, Endometrioid
/ enzymology
Cohort Studies
DNA Mismatch Repair
DNA Polymerase II
/ genetics
Endometrial Neoplasms
/ enzymology
Female
Humans
Microsatellite Instability
Middle Aged
Mutation
Neoplasm Grading
Neoplasm Metastasis
Neoplasm Recurrence, Local
/ genetics
Neoplasm Staging
Poly-ADP-Ribose Binding Proteins
/ genetics
Prognosis
Prospective Studies
POLE EDM
POLE exonuclease domain
Recurrent endometrioid endometrial adenocarcinoma
Journal
Gynecologic oncology
ISSN: 1095-6859
Titre abrégé: Gynecol Oncol
Pays: United States
ID NLM: 0365304
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
10
09
2019
revised:
23
10
2019
accepted:
25
10
2019
pubmed:
24
11
2019
medline:
25
2
2020
entrez:
24
11
2019
Statut:
ppublish
Résumé
Assess outcomes of a clinical cohort of patients with endometrioid endometrial cancer (EEC) harboring somatic POLE exonuclease domain mutations (EDMs). Patients were consented to a protocol of tumor-normal massively parallel sequencing of 410-468 cancer related genes. EECs subjected to sequencing from 2014 to 2018 were reviewed. Tumors with somatic POLE EDMs were identified. EECs were assessed for microsatellite instability (MSI) using MSIsensor and immunohistochemical analysis for mismatch repair (MMR) proteins. Of the 451 EECs sequenced, 23 had a POLE EDM (5%): 20 primary and 3 recurrent tumors sequenced. Nineteen cases (83%) were stage I/II and 4 (17%) were stages III/IV. Thirteen EECs (57%) were of FIGO grades 1/2, 10 (43%) grade 3. All patients were treated with surgery and 17 (89%) received adjuvant therapy. Five (22%) demonstrated loss of DNA MMR protein expression, none were due to Lynch syndrome. MSIsensor scores were conclusive for 21 samples: 19 were microsatellite stable and 2 MSI-high. After median follow-up of 30 months, 4/23 (17%) developed recurrences: 3 with initial grade 3 stage I and 1 with grade 1 stage III disease. One patient with grade 2 stage IV EEC had progressive disease after treatment. Patients with POLE EDM EEC have been shown to have a favorable prognosis. In this real-world cohort of patients, de novo metastatic disease and recurrences in initially uterine-confined cases were observed. Further research is warranted before incorporating the presence of POLE EDM into decision-making regarding adjuvant therapy.
Identifiants
pubmed: 31757464
pii: S0090-8258(19)31615-4
doi: 10.1016/j.ygyno.2019.10.028
pmc: PMC6980651
mid: NIHMS1544113
pii:
doi:
Substances chimiques
Poly-ADP-Ribose Binding Proteins
0
DNA Polymerase II
EC 2.7.7.7
POLE protein, human
EC 2.7.7.7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
194-202Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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