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Endometrial Carcinoma: Molecular Cytogenetics and Transcriptomic Profile
Marta Brunetti1, Ioannis Panagopoulos1, Valeria Vitelli2
1Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, 0379 Oslo, Norway.
Cancers
|July 27, 2022
Summary
This study investigated endometrial carcinomas (ECs), finding significant molecular heterogeneity. Current histological classifications may not fully capture the complex genomic and expression profiles of these tumors.
Area of Science:
- Gynecologic Oncology
- Cancer Genomics
- Molecular Pathology
Background:
- Endometrial carcinomas (ECs) are histologically classified into endometrioid and nonendometrioid types, but exhibit significant biological and clinical heterogeneity.
- The current classification scheme's imperfection necessitates further investigation into EC pathogenesis for a more refined classification.
Purpose of the Study:
- To investigate the molecular underpinnings of endometrial carcinomas by examining chromosomal aberrations, genomic imbalances, pathogenic variants, microsatellite instability, and gene/miRNA expression profiles.
- To clarify tumor pathogenesis and contribute to a more meaningful classification of endometrial carcinomas.
Main Methods:
- Analysis of 33 endometrial carcinomas for chromosomal aberrations, genomic imbalances, pathogenic variants (PTEN, PDGFRA, PIK3CA, KIT), microsatellite instability, and gene/miRNA expression.
- Comparative analysis of tumor and control samples to identify differentially expressed genes and miRNAs.
Main Results:
- Chromosome 1 rearrangements (gain of long arm) were most frequent. Pathogenic variants in PTEN (53%), PDGFRA (37%), PIK3CA (34%), and KIT (31%) were common.
- High microsatellite instability was observed in 15 ECs. Significant differences in gene expression related to carcinogenesis and immune response, along with altered miRNA expression (miR-32-5p upregulated), were identified.
- While tumors were distinct from controls, clear separation between endometrioid and nonendometrioid ECs based on genomic parameters was not achieved, indicating high heterogeneity.
Conclusions:
- Endometrial carcinomas exhibit substantial molecular heterogeneity, challenging current histological classifications.
- Further research is needed to determine if the current classification is inadequate or if specific genomic parameters require different correlation analyses to distinguish EC subtypes.
