Breiteneder-Geleff S, Soleiman A, Kowalski H, Horvat R, Amann G, Kriehuber E, Diem K, Weninger W, Tschachler E, Alitalo K, Kerjaschki D
Department of Clinical Pathology, University of Vienna, Austria.
Am J Pathol. 1999 Feb;154(2):385-94. doi: 10.1016/S0002-9440(10)65285-6.
Angiosarcomas apparently derive from blood vessel endothelial cells; however, occasionally their histological features suggest mixed origin from blood and lymphatic endothelia. In the absence of specific positive markers for lymphatic endothelia the precise distinction between these components has not been possible. Here we provide evidence by light and electron microscopic immunohistochemistry that podoplanin, a approximately 38-kd membrane glycoprotein of podocytes, is specifically expressed in the endothelium of lymphatic capillaries, but not in the blood vasculature. In normal skin and kidney, podoplanin colocalized with vascular endothelial growth factor receptor-3, the only other lymphatic marker presently available. Complementary immunostaining of blood vessels was obtained with established endothelial markers (CD31, CD34, factor VIII-related antigen, and Ulex europaeus I lectin) as well as podocalyxin, another podocytic protein that is also localized in endothelia of blood vessels. Podoplanin specifically immunolabeled endothelia of benign tumorous lesions of undisputed lymphatic origin (lymphangiomas, hygromas) and was detected there as a 38-kd protein by immunoblotting. As paradigms of malignant vascular tumors, poorly differentiated (G3) common angiosarcomas (n = 8), epitheloid angiosarcomas (n = 3), and intestinal Kaposi's sarcomas (n = 5) were examined for their podoplanin content in relation to conventional endothelial markers. The relative number of tumor cells expressing podoplanin was estimated and, although the number of cases in this preliminary study was limited to 16, an apparent spectrum of podoplanin expression emerged that can be divided into a low-expression group in which 0-10% of tumor cells contained podoplanin, a moderate-expression group with 30-60% and a high-expression group with 70-100%. Ten of eleven angiosarcomas and all Kaposi's sarcomas showed mixed expression of both lymphatic and blood vascular endothelial phenotypes. By double labeling, most podoplanin-positive tumor cells coexpressed endothelial markers of blood vessels, whereas few tumor cells were positive for individual markers only. From these results we conclude that (1) podoplanin is a selective marker of lymphatic endothelium; (2) G3 angiosarcomas display a quantitative spectrum of podoplanin-expressing tumor cells; (3) in most angiosarcomas, a varying subset of tumor cells coexpresses podoplanin and endothelial markers of blood vessels; and (4) all endothelial cells of Kaposi's sarcomas expressed the lymphatic marker podoplanin.
血管肉瘤显然起源于血管内皮细胞；然而，偶尔其组织学特征提示其起源于血液和淋巴管内皮细胞的混合。由于缺乏淋巴管内皮细胞的特异性阳性标志物，这些成分之间的精确区分一直无法实现。在此，我们通过光镜和电镜免疫组织化学提供证据表明，足突蛋白（一种约38kd的足细胞膜糖蛋白）在淋巴管内皮中特异性表达，但在血管系统中不表达。在正常皮肤和肾脏中，足突蛋白与血管内皮生长因子受体-3共定位，血管内皮生长因子受体-3是目前唯一可用的另一种淋巴管标志物。使用已确立的内皮标志物（CD31、CD34、VIII因子相关抗原和欧洲荆豆I凝集素）以及足萼蛋白（另一种也定位于血管内皮的足细胞蛋白）对血管进行互补免疫染色。足突蛋白特异性免疫标记了明确起源于淋巴管的良性肿瘤性病变（淋巴管瘤、水囊瘤）的内皮，并通过免疫印迹在其中检测到一种38kd的蛋白。作为恶性血管肿瘤的范例，对低分化（G3）普通血管肉瘤（n = 8）、上皮样血管肉瘤（n = 3）和肠道卡波西肉瘤（n = 5）的足突蛋白含量与传统内皮标志物的关系进行了研究。估计了表达足突蛋白的肿瘤细胞的相对数量，尽管这项初步研究中的病例数限于16例，但出现了一个明显的足突蛋白表达谱，可分为低表达组（0-10%的肿瘤细胞含有足突蛋白）、中表达组（30-60%）和高表达组（70-100%）。11例血管肉瘤中的10例和所有卡波西肉瘤均显示淋巴管和血管内皮表型的混合表达。通过双重标记，大多数足突蛋白阳性肿瘤细胞共表达血管内皮标志物，而仅个别标志物阳性的肿瘤细胞很少。从这些结果我们得出结论：（1）足突蛋白是淋巴管内皮的选择性标志物；（2）G3血管肉瘤显示出表达足突蛋白的肿瘤细胞的定量谱；（3）在大多数血管肉瘤中，不同比例的肿瘤细胞共表达足突蛋白和血管内皮标志物；（4）卡波西肉瘤的所有内皮细胞均表达淋巴管标志物足突蛋白。
