Abstract
Soft tissue sarcomas (STS) are malignant tumors of mesenchymal origin. A substantial portion of these tumors exhibits complex karyotypes and lack characterized chromosomal aberrations. Owing to such properties, both histopathologic and molecular classification of these tumors has been a significant challenge. This study examines the protein expression of a large number of human STS, including subtype heterogeneity, using two-dimensional gel proteomics. In addition, detailed proteome profiles of a subset of pleomorphic STS specimens using an in-depth mass-spectrometry approach identified subgroups within the leiomyosarcomas with distinct protein expression patterns. Pathways analysis indicates that key biologic nodes like apoptosis, cytoskeleton remodeling, and telomere regulation are differentially regulated among these subgroups. Finally, investigating the similarities between protein expression of leiomyosarcomas and undifferentiated pleomorphic sarcomas (UPS) revealed similar protein expression profiles for these tumors, in comparison with pleomorphic leiomyosarcomas. These results suggest that UPS tumors share a similar lineage as leiomyosarcomas and are likely to originate from different stages of differentiation from mesenchymal stem cells to smooth muscle cells.
Highlights
Soft tissue sarcomas (STS) are rare tumors of mesenchymal origin that are highly malignant and heterogeneous
Implications: These results suggest that undifferentiated pleomorphic sarcomas (UPS) tumors share a similar lineage as leiomyosarcomas and are likely to originate from different stages of differentiation from mesenchymal stem cells to smooth muscle cells
Unsupervised hierarchical clustering of the 139 tumors, based on 873 spots analyzed in 2D DIGE experiment revealed different protein expression profiles amongst the STS tumors but in general no strong clustering was observed (Supplementary data Fig. S1)
Summary
Soft tissue sarcomas (STS) are rare tumors of mesenchymal origin that are highly malignant and heterogeneous. On the basis of genetic alterations, STS are broadly divided into tumors with specific reciprocal translocations and simple karyotypes, and tumors with complex karyotypes in which specific aberrations have not been recognized [2, 3]. Differentiated sarcomas represent a diagnostic challenge as these tumors lack a typical and identifiable phenotype. The undifferentiated diagnostic category is usually considered in four broad groups: tumors with round-cell morphology, spindle-cell morphology, epithelioid morphology, and pleomorphic morphology. The latter group can be simplistically defined as the one in which the cells display marked atypia and should not be taken as synonymous of undifferentiation or biologic aggressiveness.
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