Zhang Tianshu, Koide Naohiko, Wada Yuko, Tsukioka Katsuaki, Takayama Kei, Kono Tetsuya, Kitahara Hiroto, Amano Jun
Second Department of Surgery, Shinshu University School of Medicine, Asahi, Matsumoto, Japan.
Circ J. 2003 Jan;67(1):54-60. doi: 10.1253/circj.67.54.
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.
血管生成对于肿瘤的发展和增殖不可或缺。本研究的目的是调查单核细胞趋化蛋白-1(MCP-1)和胸苷磷酸化酶(TP)的表达是否与心脏黏液瘤中的血管生成及临床病理特征相关。对17例切除的心脏黏液瘤石蜡包埋标本进行免疫组织化学染色,检测MCP-1、CC趋化因子受体-2(CCR-2)、TP、CD31和CD68。对MCP-1表达、TP表达、微血管计数(通过CD31染色确定)、巨噬细胞计数(通过CD68染色确定)以及患者的临床病理特征之间的相关性进行统计学分析。免疫组织化学分析显示,MCP-1和TP在黏液瘤细胞以及诸如浸润细胞、成纤维细胞样细胞和内皮细胞等基质细胞中表达。CCR-2在所有黏液瘤的基质浸润细胞中大量表达,偶尔也在内皮细胞中表达。在肿瘤基质中,MCP-1、TP和CCR-2的主要来源是巨噬细胞,并且在大多数黏液瘤中,MCP-1、TP和CCR-2的阳性染色部位相匹配。统计学分析显示,MCP-1阳性的黏液瘤和基质细胞以及TP阳性的黏液瘤和基质细胞的比例与微血管计数增加显著相关。MCP-1阳性的黏液瘤和基质细胞的比例与TP阳性的基质细胞的比例显著相关。肿瘤和基质MCP-1或TP高表达的黏液瘤的平均微血管计数显著高于肿瘤和基质MCP-1或TP低表达的黏液瘤。小肿瘤(直径≤55 mm)表现出高MCP-1或TP表达,并且小肿瘤中的微血管计数显著高于大黏液瘤。尽管差异不显著,但肿瘤和基质MCP-1均高表达的黏液瘤的巨噬细胞计数高于其他黏液瘤。这些结果表明,在心脏黏液瘤中,MCP-1和TP可能被视为伴随生长的重要血管生成信号。