Significance of monocyte chemotactic protein-1 and thymidine phosphorylase in angiogenesis of human cardiac myxoma

Abstract

Angiogenesis is indispensable to tumor development and proliferation. The aim of this study was to investigate whether the expression of monocyte chernotactic protein-1 (MCP-1) and of thymidine phosphorylase (TP) correlates with the angiogenesis and clinicopathologic features in cardiac myxoma. Paraffin-embedded specimens of 17 resected cardiac myxomas were immunohistochemically stained for MCP-1, CC chemokine receptor-2 (CCR-2), TP, CD31, and CD68. Correlations among MCP-1 expression, TP expression, microvessel count (determined by CD31 staining), macrophage count (determined by CD68 staining), and the clinicopathologic features of the patients were analyzed statistically. Immnohistochemical analysis revealed that MCP-1 and TP were expressed in myxoma cells, as well as in stromal cells such as infiltrating cells, fibroblast-like cells and endothelial cells. CCR-2 was abundantly expressed in stromal infiltrating cells in all myxomas and occasionally in the endothelial cells. In the tumor stroma, the major source of MCP-1, TP and CCR-2 was macrophages, and the sites of positive staining for MCP-1, TP and CCR-2 matched in most of the myxomas. Statistical analysis revealed that the proportions of MCP-1-positive myxoma and stromal cells, and TP-positive myxoma and stromal cells significantly correlated with increased microvessel count. The proportions of MCP-l 1-positive myxoma and stromal cells significantly correlated with the proportion of TP-positive stromal cells. The mean microvessel count in myxomas with both high tumor and high stromal MCP-1 or TP expression was significantly higher than that in myxomas with low tumor and low stromal MCP-1 or TP expression. Small tumors (≤55 mm in diameter) exhibited high MCP-1 or TP expression, and the microvessel count in small tumors was significantly higher than in large myxomas. Although the difference was not significant, myxomas with both high tumor and high stromal MCP-1 expression had a higher macrophage count than other myxomas. These results indicate that in cardiac myxoma, MCP-1 and TP may be regarded as important angiogenic signals accompanying growth.