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Undifferentiated Uterine Sarcoma: Molecular Subtypes Found

Normal uterine cells.

Researchers at the Karolinska Institutet in Sweden have identified new molecular subtypes of undifferentiated uterine sarcoma, a rare type of cancer that is highly deadly and has no effective treatment options.

"It is too early to propose a new treatment that will be useful for the patients today, but the study opens up new avenues for future research, which will create in time new treatment possibilities for women who suffer from these rare tumors," commented the study's senior author, Joseph Carlson, MD, PhD, Associate Professor in the Karolinska Institutet's Department of Oncology-Pathology.

The researchers studied 50 cases of undifferentiated uterine sarcoma for which detailed clinicopathological information was available. They analyzed gene expression in all 50 cases, copy number variation in 40 cases, cell morphometry in 39 cases, and protein expression in 22 cases. Their study of gene expression revealed four distinct tumor groups. An analysis of gene ontology—a bioinformatics initiative to catalogue gene function—demonstrated that these four tumor groups differ in their activation of pathways related to genital tract development, extracellular matrix (ECM), muscle function, and proliferation.

The investigators identified several factors that influence patient overall survival, including the RNA group that harbored the genetic mutation, the proportion of cells undergoing mitosis, and hormone receptor expression. Copy number variation (CNV) arrays, which analyze the number of repeats in sections of the genome, showed that each tumor subtype has its own unique set of chromosomal changes.

The most aggressive tumor subtype, the one characterized by activation of pathways related to ECM, exhibited decreased cell density and increased area of the cell nucleus. The ECM tumors showed differential expression of several ECM-related proteins—MMP-14, Collagens 1 and 6, and fibronectin—indicating that these proteins are potential biomarkers for this subtype.

In their published study in Clinical Cancer Research, the researchers conclude that molecular analysis of undifferentiated uterine sarcoma "provides novel insights into the biology, prognosis, phenotype and possible treatment of these tumors."

For More Information

Binzer-Panchal A, Hardell E, Viklund B, et al (2019). Integrated molecular analysis of undifferentiated uterine sarcomas reveals clinically relevant molecular subtypes. Clin Cancer Res. [Epub ahead of print] DOI:10.1158/1078-0432.CCR-18-2792

Image courtesy of the National Cancer Institute

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