Folpe A L, Veikkola T, Valtola R, Weiss S W
Department of Pathology, Emory University, Atlanta, Georgia, USA.
Mod Pathol. 2000 Feb;13(2):180-5. doi: 10.1038/modpathol.3880033.
Recently, a novel monoclonal antibody to vascular endothelial growth factor receptor 3 (VEGFR-3), a tyrosine kinase receptor expressed almost exclusively by lymphatic endothelium in the adult, has been shown to react with a small number of cases of Kaposi's sarcoma (KS) and cutaneous lymphangiomas. We sought to extend these studies to a large number of well-characterized vascular neoplasms to evaluate diagnostic uses of this antibody and to determine whether it defines them in a thematic fashion. Formalin-fixed, paraffin-embedded sections from 70 vascular tumors were immunostained with antibodies to VEGFR-3 von Willebrand factor (vWF), and CD31. Anti-VEGFR-3 was positive in 23 of 24 KS, 8 of 16 angiosarcomas (AS), 6 of 6 kaposiform hemangioendotheliomas, 4 of 4 Dabska tumors, and 2 of 13 hemangiomas. Positively staining angiosarcomas were characterized either by a prominent lymphocytic component, a hobnail endothelial cell similar to that encountered in the Dabska tumor, or spindled areas resembling KS. No VEGFR-3 expression was noted in any cases of epithelioid hemangioendothelioma, pyogenic granuloma, littoral angioma, or stasis dermatitis. vWF expression was seen in 10 of 13 KS; 13 of 14 AS; 4 of 5 kaposiform hemangioendotheliomas; and all Dabska tumors, hemangiomas, lymphangiomas, epithelioid hemangioendotheliomas, vascular malformations, stasis dermatitis, and splenic littoral angiomas. CD31 expression was present in 12 of 13 KS, 13 of 14 AS, and in all other cases. Expression of VEGFR-3 is a very sensitive marker of KS, kaposiform, and Dabska-type hemangioendotheliomas, suggesting that all show at least partial lymphatic endothelial differentiation. Expression of VEGFR-3 does not reliably discriminate KS from AS. However, the expression of VEGFR-3 by certain AS having Kaposi-like areas, a prominent lymphocytic infiltrate, or hobnail endothelium may define subset(s) having phenotypic, if not pathogenetic and biologic, differences.
最近，一种针对血管内皮生长因子受体3（VEGFR-3）的新型单克隆抗体已被证明可与少数卡波西肉瘤（KS）和皮肤淋巴管瘤病例发生反应。VEGFR-3是一种酪氨酸激酶受体，在成人中几乎仅由淋巴管内皮表达。我们试图将这些研究扩展到大量特征明确的血管肿瘤，以评估该抗体的诊断用途，并确定它是否以一种有规律的方式对它们进行界定。用抗VEGFR-3、血管性血友病因子（vWF）和CD31抗体对70例血管肿瘤的福尔马林固定石蜡包埋切片进行免疫染色。抗VEGFR-3在24例KS中的23例、16例血管肉瘤（AS）中的8例、6例卡波西样血管内皮瘤中的6例、4例达布斯卡瘤中的4例以及13例血管瘤中的2例呈阳性。呈阳性染色的血管肉瘤的特征要么是有显著的淋巴细胞成分，要么是有类似于达布斯卡瘤中所见的鞋钉状内皮细胞，要么是有类似KS的梭形区域。在任何上皮样血管内皮瘤、化脓性肉芽肿、滨海血管瘤或淤积性皮炎病例中均未观察到VEGFR-3表达。vWF表达见于13例KS中的10例；14例AS中的13例；5例卡波西样血管内皮瘤中的4例；以及所有达布斯卡瘤、血管瘤、淋巴管瘤、上皮样血管内皮瘤、血管畸形、淤积性皮炎和脾滨海血管瘤。CD31表达见于13例KS中的12例、14例AS中的13例以及所有其他病例。VEGFR-3的表达是KS、卡波西样和达布斯卡型血管内皮瘤的一个非常敏感的标志物，表明所有这些肿瘤至少都有部分淋巴管内皮分化。VEGFR-3的表达不能可靠地将KS与AS区分开来。然而，某些具有卡波西样区域、显著淋巴细胞浸润或鞋钉状内皮的AS中VEGFR-3的表达可能界定了具有表型差异（如果不是致病和生物学差异的话）的亚组。
