Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries -: Podoplanin as a specific marker for lymphatic endothelium
Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries -: Podoplanin as a specific marker for lymphatic endothelium
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DOI：
10.1016/s0002-9440(10)65285-6
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发表时间：
1999-02-01
影响因子：
6
通讯作者：
Kerjaschki, D
中科院分区：
文献类型：
--
作者：
Breiteneder-Geleff, S;Soleiman, A;Kerjaschki, D
血管肉瘤明显来源于血管内皮细胞；然而，偶尔它们的组织学特征提示血液和淋巴内皮的混合起源。在缺乏淋巴内皮特异性阳性标记物的情况下，这些成分之间的精确区分是不可能的。在这里，我们通过光镜和电镜免疫组织化学提供了证据，证明podoplanin，一种类似于足细胞的38-kd膜糖蛋白，在淋巴毛细血管的内皮中特异性表达，而不是在血管中。在正常皮肤和肾脏中，podoplanin与血管内皮生长因子受体-3共定位。这是目前唯一可用的淋巴标记物。利用已建立的内皮标记物（CD31、CD34、viii因子相关抗原、欧paeus Ulex I凝集素）和另一种同样定位于血管内皮的足细胞蛋白podocalyxin对血管进行互补免疫染色。Podoplanin特异性免疫标记无争议淋巴起源的良性肿瘤病变（淋巴管瘤，水瘤）的内皮，并通过免疫印迹检测到其为38-kd蛋白。作为恶性血管肿瘤的典型，低分化（G3）常见血管肉瘤（n = 8），上皮血管肉瘤（n = 3）和肠卡波西肉瘤（n = 5）检测了其Podoplanin含量与常规内皮标志物的关系。估计了表达podoplanin的肿瘤细胞的相对数量，虽然本初步研究的病例数限制在16例，但出现了一个明显的podoplanin表达谱，可分为低表达组（0-10%的肿瘤细胞含有podoplanin），中等表达组（30-60%）和高表达组（70-100%）。11例血管肉瘤中的10例和所有卡波西氏肉瘤均表现为淋巴和血管内皮表型的混合表达。通过双标记，大多数podoplanin阳性肿瘤细胞共表达血管内皮标志物，而少数肿瘤细胞仅表达单个标志物。从这些结果我们得出结论：(1)podoplanin是淋巴内皮的选择性标志物；(2) G3型血管肉瘤表现出表达podoplanin的肿瘤细胞的定量谱；(3)在大多数血管肉瘤中，不同的肿瘤细胞亚群共同表达足平面蛋白和血管内皮标志物；(4)卡波西肉瘤内皮细胞均表达淋巴标记物podoplanin。
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 similar to 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.