Sun Baocun, Zhang Shiwu, Zhao Xiulan, Zhang Wei, Hao Xishan
Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin 300060, PR China.
Int J Oncol. 2004 Dec;25(6):1609-14.
Increased vasculogenesis must occur for tumors to develop and be maintained. Normally, vascular networks are composed of tube structures lined with endothelial cells. However, the vascular networks that form around some highly aggressive cancers possess a distinct tubular structure, resulting from a process called vasculogenic mimicry (VM) that does not have endothelial cells. In these tubes, the tumor cells function as endothelial cells. VM has been found in several different types of cancers such as melanoma, breast cancer, prostate cancer, and ovarian cancer. We hypothesized that it also plays a role in the development and metastasis of sarcomas, which are typically aggressive tumors. We used immunohistochemical analyses and electron microscopy to identify VM channels in 81 synovial sarcomas (SSs), 37 mesothelial sarcomas (MSs), 69 alveolar rhabdomyosarcomas (ARs), and 190 melanomas, which were used as a comparison group. The presence of red blood cells in the vessels was also used as a criterion for VM. Because VM is generally believed to be associated with aggressive cancers, we tested whether the presence of VM channel correlated with patient survival. We detected VM channels in 11 of 81 SSs (13.6%), 10 of 37 MSs (27.0%), 13 of 69 ARs (18.8%), and 10 of 190 melanomas (5.3%). The VM channels were not distributed uniformly in the tumor tissues but appeared in patches. In addition, VM channels were most frequently observed in the boundary regions between the tumor and adjacent normal tissues. The tumor cells around the VM tubes frequently stained positive for collagen IV and CD31 and were also PAS-positive. In contrast, tumors that lack VM channels generally also lack these markers. Our studies of the correlation of VM with patient survival also showed that VM correlated with shorter survival in patients with MS (P=0.03), AR (P=0.03), and melanoma (P=0.04), but not with SS (P=0.76). Our studies demonstrated that VM channels are a clinically important phenotype in sarcomas and melanomas. Our findings also suggested that a subpopulation of tumor cells possess features of both endothelial cells that line the vessels and mesenchymal cells that secrete the extracellular matrix required for the vascular infrastructure.
肿瘤的发生和维持必须有血管生成增加。正常情况下，血管网络由内衬内皮细胞的管状结构组成。然而，一些高侵袭性癌症周围形成的血管网络具有独特的管状结构，这是由一种名为血管生成拟态（VM）的过程导致的，该过程中不存在内皮细胞。在这些管道中，肿瘤细胞发挥着内皮细胞的功能。VM已在多种不同类型的癌症中被发现，如黑色素瘤、乳腺癌、前列腺癌和卵巢癌。我们推测它在肉瘤的发生和转移中也起作用，肉瘤通常是侵袭性肿瘤。我们使用免疫组织化学分析和电子显微镜在81例滑膜肉瘤（SS）、37例间皮肉瘤（MS）、69例肺泡横纹肌肉瘤（AR）和190例黑色素瘤中识别VM通道，黑色素瘤用作对照组。血管中红细胞的存在也被用作VM的一个标准。由于一般认为VM与侵袭性癌症相关，我们测试了VM通道的存在是否与患者生存率相关。我们在81例SS中的11例（13.6%）、37例MS中的10例（27.0%）、69例AR中的13例（18.8%）和190例黑色素瘤中的10例（5.3%）中检测到VM通道。VM通道在肿瘤组织中分布不均匀，而是呈斑块状出现。此外，VM通道最常出现在肿瘤与相邻正常组织之间的边界区域。VM管周围 的肿瘤细胞胶原IV和CD31常呈阳性染色，且PAS也呈阳性。相比之下，缺乏VM通道的肿瘤通常也缺乏这些标志物。我们对VM与患者生存率相关性的研究还表明，VM与MS（P = .03）、AR（P = .03）和黑色素瘤（P = .04）患者的较短生存期相关，但与SS无关（P = .76）。我们的研究表明，VM通道是肉瘤和黑色素瘤中的一种临床重要表型。我们的研究结果还表明，肿瘤细胞的一个亚群具有内衬血管的内皮细胞和分泌血管基础设施所需细胞外基质的间充质细胞的特征。
