Endometrial carcinomas with ambiguous histology often harbor TP53 mutations.
Ambiguous endometrial carcinoma
Survival
TP53
Whole-exome sequencing
Journal
Virchows Archiv : an international journal of pathology
ISSN: 1432-2307
Titre abrégé: Virchows Arch
Pays: Germany
ID NLM: 9423843
Informations de publication
Date de publication:
05 Sep 2024
05 Sep 2024
Historique:
received:
06
07
2024
accepted:
25
08
2024
revised:
01
08
2024
medline:
5
9
2024
pubmed:
5
9
2024
entrez:
5
9
2024
Statut:
aheadofprint
Résumé
The objective of the present study was to characterize the molecular features of endometrial carcinomas with ambiguous histology. Eighteen carcinomas that could not be conclusively typed based on morphology and immunohistochemistry underwent analysis of mismatch repair (MMR) status, microsatellite status, and whole-exome sequencing. None of the tumors had pathogenic POLE mutation. Twelve tumors (67%) were microsatellite stable, and 6 (33%) had microsatellite instability. Fourteen tumors (78%) harbored TP53 mutations, and 2 (11%) had mutations in MMR genes. Eleven carcinomas (61%) were classified as copy number high and 7 (39%) as MSI-hypermutated, the latter including 3 tumors with TP53 mutation who concomitantly had MSI or mutation in a MMR gene. Other mutations that were found in > 1 tumor affected MUC16 (7 tumors), PIK3CA (6 tumors), PPP2R1A (6 tumors), ARID1A (5 tumors), PTEN (5 tumors), FAT1 (4 tumors), FAT4 (3 tumors), BRCA2 (2 tumors), ERBB2 (2 tumors), FBXW7 (2 tumors), MET (2 tumors), MTOR (2 tumors), JAK1 (2 tumors), and CSMD3 (2 tumors). At the last follow-up (median = 68.6 months), 8 patients had no evidence of disease, 1 patient was alive with disease, 8 patients were dead of disease, and 1 patient died of other cause. In conclusion, based on this series, the molecular landscape of endometrial carcinomas with ambiguous histology is dominated by TP53 mutations and the absence of POLE mutations, with heterogeneous molecular profile with respect to other genes. A high proportion of these tumors is clinically aggressive.
Identifiants
pubmed: 39235515
doi: 10.1007/s00428-024-03912-7
pii: 10.1007/s00428-024-03912-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s).
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