Diagnostic and prognostic gene expression signatures in 177 soft tissue sarcomas: hypoxia-induced transcription profile signifies metastatic potential.

[pleomorphic liposarcoma]

Soft tissue sarcoma (STS ) diagnosis is challenging because of a multitude of histopathological subtypes , different genetic characteristics , and frequent intratumoral pleomorphism . One -third of STS metastasize and current risk-stratification is suboptimal , therefore , novel diagnostic and prognostic markers would be clinically valuable . We assessed the diagnostic and prognostic value of array-based gene expression profiles using 27 k cDNA microarrays in 177 , mainly high -grade , STS of 13 histopathological subtypes .U nsupervised analysis resulted in two major clusters--one mainly containing STS characterized by type -specific genetic alterations and the other with a predominance of genetically complex and pleomorphic STS . Synovial sarcomas , myxoid /round -cell liposarcomas , and gastrointestinal stromal tumors clustered tightly within the former cluster and discriminatory signatures for these were characterized by developmental genes from the EGFR , FGFR , Wnt , Notch , Hedgehog , RAR and KIT signaling pathways . The more pleomorphic STS subtypes , e .g . leiomyosarcoma , malignant fibrous histiocytoma /undifferentiated pleomorphic sarcoma and dedifferentiated /pleomorphic liposarcoma , were part of the latter cluster and were characterized by relatively heterogeneous profiles , although subclusters herein were identified . A prognostic signature partly characterized by hypoxia-related genes was identified among 89 genetically complex pleomorphic primary STS and could , in a multivariate analysis including established prognostic markers , independently predict the risk of metastasis with a hazard ratio of 2 .2 (P = 0 .04 ).Diagnostic gene expression profiles linking signaling pathways to the different STS subtypes were demonstrated and a hypoxia-induced metastatic profile was identified in the pleomorphic , high -grade STS . These findings verify diagnostic utility and application of expression data for improved selection of high -risk STS patients .

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pleomorphic liposarcoma

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