Gene Expression Profiling Associated with the Progression of Classic Kaposi's Sarcoma

Abstract

Although Kaposi's sarcoma (KS) gene expression profile is closer to lymphatic (LEC) rather than blood vascular endothelial cells (BEC), uncertainty still surrounds the cellular origin of KS. To follow KS progression from early to late (nodular) stage, and characterize the molecular fingerprinting associated with each stage, gene arrays were used to compare gene expression profile of 9 skin samples of classic KS (4 Early, 2 Mixed, and 3 Nodular CKS samples) to 4 normal samples. Results for selected genes were validated by Real-time (RT) PCR and immunohistochemistry. Genes regulating immune and defense responses, angiogenesis, apoptosis and proliferation were differentially expressed in different KS stages compared to normal skin. Hierarchical clustering separated normal skin from KS with a clear gradient from early to nodular KS lesions. The gene expression level of endothelium markers, metalloproteinases, angiogenic factors and chemokines, gradually increased from normal through all KS stages. The expression of LEC genes highly increased from early to nodular KS. In the initiation phase we noticed a higher expression of growth factors, as compared to progressive stages. LEC and BEC markers co-exist in “KS expression signature”, although the LEC signature prevailed. Our results also show a complex environment of inflammatory cells and chemokines during KS evolution. A pathogenic hypothesis where cellular hyperproliferation is driven by local expression of chemokines and growth factors without clonal expansion of cells is suggested.