Platelet-derived growth factor-A and vascular endothelial growth factor-C contribute to the development of pulmonary tumor thrombotic microangiopathy in gastric cancer
Platelet-derived growth factor-A and vascular endothelial growth factor-C contribute to the development of pulmonary tumor thrombotic microangiopathy in gastric cancer
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DOI：
10.1007/s00428-013-1403-7
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发表时间：
2013-05-01
期刊：
影响因子：
3.5
通讯作者：
Fukayama, Masashi
中科院分区：
文献类型：
--
作者：
Abe, Hiroyuki;Hino, Rumi;Fukayama, Masashi
摘要肺部肿瘤血栓性微血管病变是一种罕见但致命的并发症，在癌症患者中，尤其是胃癌患者。其特征是癌细胞栓塞伴显著内膜增生。在本研究中，我们试图阐明肺肿瘤血栓性微血管病的发病机制，特别是肿瘤细胞特异性血管生成因子在肺动脉中的作用。本文回顾了51例胃癌的尸检资料，分析了肺肿瘤血栓性微血管病变和无内膜增生的肺肿瘤细胞栓子。比较两组的病理及免疫组化特点。在8例肌性肺动脉中，注意到肿瘤血栓性微血管病，在3例肺肿瘤栓塞中注意到无内膜增生。肺肿瘤血栓性微血管病的组织学特征包括小巢或单个癌细胞伴内膜增生，而肺肿瘤栓子以大细胞巢为主。免疫组化结果显示，在肺肿瘤血栓性微血管病中，癌细胞表达血小板源性生长因子-A（7/8例）和血管内皮生长因子-C（8/8例）的频率高于肺肿瘤栓子（0/3和1/3; P = 0.02和P = 0.055，分别）。组织因子、血管内皮生长因子-A和-D、骨桥蛋白、成纤维细胞生长因子-2和血小板源性生长因子-B的表达在两组中相似。血小板源性生长因子-A和血管内皮生长因子-C可能诱导肺动脉内膜增生，并参与肺肿瘤血栓性微血管病的发生。
Pulmonary tumor thrombotic microangiopathy is a rare but lethal complication in cancer-bearing patients, particularly those with gastric cancer. It is characterized by cancer cell emboli with marked intimal proliferation. In the present study, we tried to elucidate the pathogenesis of pulmonary tumor thrombotic microangiopathy, notably angiogenic factors specific for cancer cells lodged in pulmonary arteries. An autopsy series of gastric cancer (51 cases) was reviewed for pulmonary tumor thrombotic microangiopathy and pulmonary tumor cell emboli without intimal proliferation. Pathological and immunohistochemical characteristics were compared between two groups. In eight cases in muscular pulmonary arteries, tumor thrombotic microangiopathy was noted, and in three cases pulmonary tumor emboli without intimal proliferation was noted. Histological features of pulmonary tumor thrombotic microangiopathy included small nests or single cancer cells accompanied by intimal proliferation, whereas in pulmonary tumor emboli large cell nests prevailed. By immunohistochemistry, in pulmonary tumor thrombotic microangiopathy, cancer cells expressed platelet-derived growth factor-A (7/8 cases) and vascular endothelial growth factor-C (8/8) more frequently than in pulmonary tumor emboli (0/3 and 1/3; P = 0.02 and P = 0.055, respectively). Expression of tissue factor, vascular endothelial growth factor-A and -D, osteopontin, fibroblast growth factor-2, and platelet-derived growth factor-B was similar in both groups. Platelet-derived growth factor-A and vascular endothelial growth factor-C might induce intimal proliferation in pulmonary arteries and contribute to the development of pulmonary tumor thrombotic microangiopathy.