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

Circ J. 2003 Jan;67(1):54-60. doi: 10.1253/circj.67.54.

Abstract

Angiogenesis is indispensable to tumor development and proliferation. The aim of this study was to investigate whether the expression of monocyte chemotactic 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. Immunohistochemical 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-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 (< or =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.

MeSH terms

  • Blood Vessels / pathology
  • Cell Count
  • Chemokine CCL2 / metabolism*
  • Heart Neoplasms / complications*
  • Heart Neoplasms / metabolism*
  • Heart Neoplasms / pathology
  • Humans
  • Immunohistochemistry / methods
  • Macrophages / pathology
  • Microcirculation
  • Middle Aged
  • Myxoma / complications*
  • Myxoma / metabolism*
  • Myxoma / pathology
  • Neovascularization, Pathologic / etiology*
  • Receptors, CCR2
  • Receptors, Chemokine / metabolism
  • Staining and Labeling
  • Thymidine Phosphorylase / metabolism*
  • Tissue Distribution

Substances

  • CCR2 protein, human
  • Chemokine CCL2
  • Receptors, CCR2
  • Receptors, Chemokine
  • Thymidine Phosphorylase