Gene expression profiling in sarcomas

Sarcomas are a heterogeneous group of malignant mesenchymal tumors of difficult classification. There is considerable variability in both histological appearance and responsiveness to therapy. Their overall poor clinical prognosis is reflected by the fact that >65% of patients suffering retroperitoneal soft tissue sarcoma die within 5 years [Heslin MJ, et al. Prognostic factors associated with long-term survival for retroperitoneal sarcoma: implications for management. J Clin Oncol 1997;15(8):2832-9]. A greater understanding of the biology of sarcomas is needed in order to increase the potential for identifying new therapeutic targets and strategies. Microarray analysis permits a global approach to gene expression analysis of thousands of genes at the same time and has proven to be useful for further molecular characterization of tumor tissue and cell lines. This article provides a comprehensive review of possible new biomarkers identified in gene expression studies of sarcomas. These markers give new insight into the pathogenesis of sarcomas, such as malignant fibrous histiocytoma [Lee YF, et al. Molecular classification of synovial sarcomas, leiomyosarcomas and malignant fibrous histiocytomas by gene expression profiling. Br J Cancer 2003;88(4):510-5], allow a further subclassifcation of tumors like calponin-positive and calponin-negative leiomyosarcoma, or may help to predict treatment responsiveness and prognosis in patients based on an individual gene expression pattern. In some studies candidate targets for possible new treatment strategies were identified. For instance newly identified markers such as ERBB2 [Allander SV, et al. Expression profiling of synovial sarcoma by cDNA microarrays: association of ERBB2, IGFBP2, and ELF3 with epithelial differentiation. Am J Pathol 2002;161(5):1587-95] and EGFR [Nielsen TO, et al. Molecular characterization of soft tissue tumours: a gene expression study. Lancet 2002;359(9314):1301-7] might lead to the possible therapeutic use of Trastuzumab, Gefitinib or Cetuximab in synovial sarcoma, comparable to the use of tyrosine kinase inhibitor STI (Gleevec) that is the standard treatment today of CD117-positive gastrointestinal stromal tumors.