Molecular profiling identifies synchronous endometrial and ovarian cancers as metastatic endometrial cancer with favorable clinical outcome.
Adult
Aged
Aged, 80 and over
Clonal Evolution
DNA Mismatch Repair
DNA Polymerase II
/ genetics
Databases, Genetic
Endometrial Neoplasms
/ genetics
Female
High-Throughput Nucleotide Sequencing
Humans
Middle Aged
Mutation
Neoplasms, Multiple Primary
/ genetics
Ovarian Neoplasms
/ genetics
Poly-ADP-Ribose Binding Proteins
/ genetics
Prognosis
Retrospective Studies
Tumor Suppressor Protein p53
/ genetics
clonality
endometrial neoplasms
molecular pathology
ovarian neoplasms
synchronous tumors
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
15 07 2020
15 07 2020
Historique:
received:
02
01
2020
revised:
17
01
2020
accepted:
22
01
2020
pubmed:
6
2
2020
medline:
9
3
2021
entrez:
6
2
2020
Statut:
ppublish
Résumé
Synchronous primary endometrial and ovarian cancers (SEOs) represent 10% of all endometrial and ovarian cancers and are assumed to develop as independent entities. We investigated the clonal relationship between endometrial and ovarian carcinomas in a large cohort classified as SEOs or metastatic disease (MD). The molecular profiles were compared to The Cancer Genome Atlas (TCGA) data to explore primary origin. Subsequently, the molecular profiles were correlated with clinical outcome. To this extent, a retrospective multicenter study was performed comparing patients with SEOs (n = 50), endometrial cancer with synchronous ovarian metastasis (n = 19) and ovarian cancer with synchronous endometrial metastasis (n = 20). Targeted next-generation sequencing was used, and a clonality index was calculated. Subsequently, cases were classified as POLE mutated, mismatch repair deficient (MMR-D), TP53-wild-type or TP53-mutated. In 92% of SEOs (46/50), the endometrial and concurrent ovarian carcinoma shared at least one somatic mutation, with a clonality index above 0.95, supporting a clonal origin. The SEO molecular profiles showed striking similarities with the TCGA endometrial carcinoma set. SEOs behaved distinctly different from metastatic disease, with a superior outcome compared to endometrial MD cases (p < 0.001) and ovarian MD cases (p < 0.001). Classification according to the TCGA identified four groups with different clinical outcomes. TP53 mutations and extra-utero-ovarian disease were independent predictors for poor clinical outcome. Concluding, SEOs were clonally related in an overwhelming majority of cases and showed a favorable prognosis. Their molecular profile implied a primary endometrial origin. TP53 mutation and extra-utero-ovarian disease were independent predictors for outcome, and may impact adjuvant systemic treatment planning.
Identifiants
pubmed: 32022266
doi: 10.1002/ijc.32907
pmc: PMC7317735
doi:
Substances chimiques
Poly-ADP-Ribose Binding Proteins
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
DNA Polymerase II
EC 2.7.7.7
POLE protein, human
EC 2.7.7.7
Types de publication
Comparative Study
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
478-489Informations de copyright
© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
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