Endometrial Stem/Progenitor cell (ES/PC) Marker Expression Profile in Adenosarcoma and Endometrial Stromal Sarcoma.


Journal

Cancer treatment and research communications
ISSN: 2468-2942
Titre abrégé: Cancer Treat Res Commun
Pays: England
ID NLM: 101694651

Informations de publication

Date de publication:
2021
Historique:
received: 15 10 2020
revised: 28 02 2021
accepted: 23 03 2021
pubmed: 11 4 2021
medline: 31 12 2021
entrez: 10 4 2021
Statut: ppublish

Résumé

The uterus is one of the most dynamic organs in the human body, and this dynamic homeostasis is supported by endometrial stem/progenitor cells (ES/PCs), which are heterogeneous in their phenotype and degree of differentiation. ES/PCs are generally localized in the endometrial stroma, the site of origin for adenosarcoma and endometrial stromal sarcoma (ESS). Subsets of ESSs and adenosarcomas harbor SUZ12 or DICER1 gene alterations, two genes with roles in embryonic stem cell biology. However, the possible contribution of ES/PCs to tumorigenesis is unexplored. We examined the expression of eleven ES/PC markers, along with three proteins expressed in the mature endometrial stroma (ER, PR and CD10) in 60 uterine tumors (24 low-, 11 high-grade ESS, 25 adenosarcomas). Protein expression profiles were assessed by unsupervised hierarchical clustering. miRNA expression profiles were examined in a subset of adenosarcoma with/without DICER1 mutations, using the NanoString platform. ES/PC markers were variably expressed, and the tumors exhibited limited immunophenotypic resemblance to different ES/PCs. Within the ESSs, the ES/PC marker clustering pattern was prognostic for both overall and disease-free survival. Comparing adenosarcomas and ESSs, most high-grade ESSs clustered with one another, while low-grade ESSs and adenosarcomas tended to cluster with one another. Among the adenosarcomas, the miRNA expression profiles were varied with respect to the DICER1 mutation status, with pathway analysis pointing to dysregulated signal transduction and stem cell biology. ESSs and adenosarcomas exhibit varying immunophenotypic resemblance to ES/PCs. These expression profiles have prognostic implications and may be genetically driven.

Sections du résumé

BACKGROUND
The uterus is one of the most dynamic organs in the human body, and this dynamic homeostasis is supported by endometrial stem/progenitor cells (ES/PCs), which are heterogeneous in their phenotype and degree of differentiation. ES/PCs are generally localized in the endometrial stroma, the site of origin for adenosarcoma and endometrial stromal sarcoma (ESS). Subsets of ESSs and adenosarcomas harbor SUZ12 or DICER1 gene alterations, two genes with roles in embryonic stem cell biology. However, the possible contribution of ES/PCs to tumorigenesis is unexplored.
METHOD
We examined the expression of eleven ES/PC markers, along with three proteins expressed in the mature endometrial stroma (ER, PR and CD10) in 60 uterine tumors (24 low-, 11 high-grade ESS, 25 adenosarcomas). Protein expression profiles were assessed by unsupervised hierarchical clustering. miRNA expression profiles were examined in a subset of adenosarcoma with/without DICER1 mutations, using the NanoString platform.
RESULTS
ES/PC markers were variably expressed, and the tumors exhibited limited immunophenotypic resemblance to different ES/PCs. Within the ESSs, the ES/PC marker clustering pattern was prognostic for both overall and disease-free survival. Comparing adenosarcomas and ESSs, most high-grade ESSs clustered with one another, while low-grade ESSs and adenosarcomas tended to cluster with one another. Among the adenosarcomas, the miRNA expression profiles were varied with respect to the DICER1 mutation status, with pathway analysis pointing to dysregulated signal transduction and stem cell biology.
CONCLUSIONS
ESSs and adenosarcomas exhibit varying immunophenotypic resemblance to ES/PCs. These expression profiles have prognostic implications and may be genetically driven.

Identifiants

pubmed: 33838572
pii: S2468-2942(21)00061-7
doi: 10.1016/j.ctarc.2021.100363
pii:
doi:

Substances chimiques

Antigens, CD 0
Biomarkers, Tumor 0
LGR5 protein, human 0
MSI1 protein, human 0
Membrane Glycoproteins 0
MicroRNAs 0
Neoplasm Proteins 0
Nerve Tissue Proteins 0
RNA, Messenger 0
RNA-Binding Proteins 0
Receptors, Estrogen 0
Receptors, G-Protein-Coupled 0
Receptors, Progesterone 0
SUSD2 protein, human 0
SUZ12 protein, human 0
Transcription Factors 0
ST3GAL3 protein, human EC 2.4.99.-
Sialyltransferases EC 2.4.99.-
DICER1 protein, human EC 3.1.26.3
Ribonuclease III EC 3.1.26.3
DEAD-box RNA Helicases EC 3.6.4.13

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

100363

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Auteurs

Ju-Yoon Yoon (JY)

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Pathology, St. Michael's Hospital, Toronto, ON, Canada. Electronic address: juyoon.yoon@utoronto.ca.

Leanne de Kock (L)

Department of Human Genetics, McGill University, Montréal, Québec, Canada; Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montréal, Québec, Canada; Research Institute of the McGill University Health Centre, Montréal, Québec, Canada.

Colin J R Stewart (CJR)

School for Women's and Infants' Health, University of Western Australia, Perth, WA, Australia.

W Glenn McCluggage (WG)

Department of Pathology, Belfast Health and Social Care Trust, Belfast, United Kingdom.

William D Foulkes (WD)

Department of Human Genetics, McGill University, Montréal, Québec, Canada; Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montréal, Québec, Canada; Research Institute of the McGill University Health Centre, Montréal, Québec, Canada.

Blaise A Clarke (BA)

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Pathology, Toronto General Hospital, Toronto, ON, Canada.

Marjan Rouzbahman (M)

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Pathology, Toronto General Hospital, Toronto, ON, Canada.

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Classifications MeSH