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

Cancer Treat Res Commun. 2021;27:100363. doi: 10.1016/j.ctarc.2021.100363. Epub 2021 Mar 31.

Abstract

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.

Keywords: Adenosarcoma; Endometrial stem/progenitor cells; Endometrial stromal sarcoma; Tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosarcoma / genetics
  • Adenosarcoma / metabolism*
  • Antigens, CD / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • DEAD-box RNA Helicases / genetics*
  • Disease-Free Survival
  • Endometrial Neoplasms / metabolism*
  • Endometrial Neoplasms / pathology
  • Endometrium / metabolism
  • Endometrium / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Immunophenotyping
  • Membrane Glycoproteins / metabolism
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs / metabolism
  • Middle Aged
  • Mutation
  • Neoplasm Grading
  • Neoplasm Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Progesterone / metabolism
  • Ribonuclease III / genetics*
  • Sarcoma, Endometrial Stromal / metabolism*
  • Sarcoma, Endometrial Stromal / pathology
  • Sialyltransferases / metabolism
  • Signal Transduction / genetics
  • Survival Rate
  • Transcription Factors / genetics
  • Uterine Neoplasms / genetics
  • Uterine Neoplasms / metabolism*

Substances

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

Supplementary concepts

  • Adenosarcoma of the uterus