Endometrial carcinomas with ambiguous histology often harbor TP53 mutations.

Autor: Davidson B; Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310, Oslo, Norway. bend@medisin.uio.no.; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, N-0316, Oslo, Norway. bend@medisin.uio.no., Teien Lande K; Department of Cancer Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310, Oslo, Norway., Nebdal D; Department of Cancer Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310, Oslo, Norway., Nesbakken AJ; Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310, Oslo, Norway., Holth A; Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310, Oslo, Norway., Lindemann K; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, N-0316, Oslo, Norway.; Section for Gynecologic Oncology, Division of Surgical Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway., Zahl Eriksson AG; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, N-0316, Oslo, Norway.; Section for Gynecologic Oncology, Division of Surgical Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway., Sørlie T; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, N-0316, Oslo, Norway. tsorlie@rr-research.no.; Department of Cancer Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310, Oslo, Norway. tsorlie@rr-research.no.
Jazyk: angličtina
Zdroj: Virchows Archiv : an international journal of pathology [Virchows Arch] 2024 Sep 05. Date of Electronic Publication: 2024 Sep 05.
DOI: 10.1007/s00428-024-03912-7
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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