Malignant fibrous histiocytoma: a proposed cellular origin and identification of its characterizing gene transcripts

Although malignant fibrous histiocytoma (MFH) is one of the most diffuse and highly aggressive tumors among soft tissue sarcomas in adults, it is poorly characterized from the molecular point of view. The overt lack of expression of phenotypic markers in MFH cells and the hypothesis that MFH may originate from transformed multipotent stem/progenitor cells with mesenchymal features has led us to investigate this notion and search for ‘MFH-specific’ genes. To address this problem, we have undertaken a differential display-based three-pair comparative mRNA profiling of bone-marrow derived mesenchymal stem cells (MSC) and cells isolated by primary MFH, leiomyosarcoma and smooth muscle cells, fibrosarcoma and dermal fibroblasts. This approach highlighted pair-wise analogies in gene expression patterns between matched tumor and healthy cells and yielded direct access to 43 genes differentially expressed between MSC and MFH cells. Eleven of the identified genes were selected for comparative evaluation of their expression levels in other sarcoma types, as well as potential markers for the detection of circulating tumor cells. Several of these genes defined the stem/progenitor versus MFH cell and some of them have the potential to be exploited for disclosure of circulating sarcoma cells. The striking similarity in the gene expression patterns observed in the two cell types was further corroborated by a remarkable similarity in the cell phenotypic markers that these cells expressed ex vivo. The findings open now the possibility to examine, also functionally, genes not previously known to be implicated in MFH development and strengthen the hypothesis that MFH originates from a mesenchymal progenitor cell.