RESULTS: H & E stained sections revealed; prominent angiogenesis with proliferating vascular network associated with lymphocytes and plasma cells; and proliferating KS cells of mixed morphology with a predominant spindle cell component. Immunolocalization revealed the highest level of MMP expression was at sites of vascular invasion adjacent to vascular walls and in the presence of infiltrating inflammatory cells. Mast cell accumulation and degranulation plays a role at the tumor periphery and near vascular walls. High levels of MMPs expression was associated with morphological heterogeneity within the tumor cell population. KS cells with spindle morphology appeared to contribute with high levels of MMP-1, -2, -3, -9, and -13, and low level of MMP-7 and -14 expression. The stromal contribution, is very significant in the expression of MMP-1, -3, -9 and -14, but low MMP-2 and 13 at sites of inflammation and vascular invasion. Endothelial cells contribute by MMP-1, -3, -9, -14 and slight MMP-2, -7 and -13 expression. Conclusion: The in vivo expression of MMPs in KS is dictated by multifactorial interactions between KS cells, stromal fibroblasts and mast cells, inflammatory infiltrate, and finally by the angiogenic activity. (Supported in part by NIDCR grant DE-07258).