Gene expression analysis of soft tissue sarcomas: Characterization and reclassification of malignant fibrous histiocytoma

Cancer Transcriptome Project, National Cancer Center Research Institute, Tokyo, Japan.
Modern Pathology (Impact Factor: 6.36). 04/2007; 20(7):749-759. DOI: 10.1038/modpathol.3800794

ABSTRACT In soft tissue sarcomas, the diagnosis of malignant fibrous histiocytoma (MFH) has been a very controversial issue, and MFH is now considered to be reclassified into pleomorphic subtypes of other sarcomas. To characterize MFH genetically, we used an oligonucleotide microarray to analyze gene expression in 105 samples from 10 types of soft tissue tumors. Spindle cell and pleomorphic sarcomas, such as dedifferentiated liposarcoma, myxofibrosarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumor (MPNST), fibrosarcoma and MFH, showed similar gene expression patterns compared to other tumors. Samples from those five sarcoma types could be classified into respective clusters based on gene expression by excluding MFH samples. We calculated distances between MFH samples and other five sarcoma types (dedifferentiated liposarcoma, myxofibrosarcoma, leiomyosarcoma, MPNST and fibrosarcoma) based on differentially expressed genes and evaluated similarities. Three of the 21 MFH samples showed marked similarities to one of the five sarcoma types, which were supported by histological findings. Although most of the remaining 18 MFH samples showed little or no histological resemblance to one of the five sarcoma types, 12 of them showed moderate similarities in terms of gene expression. These results explain the heterogeneity of MFH and show that the majority of MFHs could be reclassified into pleomorphic subtypes of other sarcomas. Taken together, gene expression profiling could be a useful tool to unveil the difference in the underlying molecular backgrounds, which leads to a rational taxonomy and diagnosis of a diverse group of soft tissue sarcomas.Keywords: gene expression, malignant fibrous histiocytoma, myxofibrosarcoma, soft tissue sarcoma, reclassification, undifferentiated pleomorphic sarcoma

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Available from: Hiro Takahashi, Aug 03, 2015
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    • "(B) Top: relative expression of CDK4, MDM2, NUP107, and OS9 in 15 WD/DDLPS samples compared to a pool of 116 other sarcomas. Bottom: the same analysis using an independent set of 105 sarcomas, including 18 WD/DDLPS samples (National Center for Biotechnology Information Data Set Browser record GDS2736; Nakayama et al., 2007). Box-and-whisker plots show log 2 gene expression distribution (**** p < 0.0001, two-tailed t test). "
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    Cancer Cell 11/2014; 26(5):653-667. DOI:10.1016/j.ccell.2014.09.010 · 23.89 Impact Factor
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    • "Nakayama data—A data set consisting of 105 samples from 10 types of soft tissue tumors, each with 22,283 gene expression measurements (Nakayama et al. 2007). We limited the analysis to five tumor types for which at least 15 samples were present in the data; the resulting subset of the data contained 86 samples. "
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    • "Several prior studies have performed gene expression profiling on relatively small numbers (n=3–13) of LMS samples (Baird et al., 2005; Henderson et al., 2005; Nakayama et al., 2007; Nielsen et al., 2002; Quade et al., 2004; Ren et al., 2003; Segal et al., 2003; Shmulevich et al., 2002; Skubitz and Skubitz, 2003). Due to the small number of cases in each study it is difficult to draw conclusions on the heterogeneity within LMS based on these data. "
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