Miettinen M, Fetsch J F
Armed Forces Institute of Pathology, Department of Soft Tissue Pathology, Washington, DC 20306-6000, USA.
Hum Pathol. 2000 Sep;31(9):1062-7. doi: 10.1053/hupa.2000.9843.
Vascular endothelial cells are specialized mesenchyme-derived epithelial-like lining cells which are the essential participants in benign and malignant vascular tumors. Although endothelia in lower animals often express keratins (K), human endothelia are generally K negative and vimentin-positive. However, K expression has been noted in some endothelia and in some epithelioid vascular tumors. In this study, we systematically examined normal human vascular endothelia and a spectrum of human vascular tumors (n = minimum of 137 tumors with each marker) for simple epithelial keratin polypeptides of the Moll catalogue (K7, K8, K18, and K19). Selected vascular tumors were also evaluated with antibodies to K14 and the monoclonal antibody 34betaE12 that recognizes several keratins of stratified epithelia. Endothelia of normal veins, venules, and lymphatics commonly exhibited focal positivity for K7 and K18, whereas K8, K14, and K19 were not seen in non-neoplastic endothelia with the antibodies used. Lymphangiomas (6 of 7) and venous hemangiomas (6 of 13) often showed K7-positive endothelial cells; K18 was detected less commonly, whereas K8 and K19 were not detected. Epithelioid hemangioendotheliomas (EHEs) showed K7 and K18 expression in the majority of cases (50% and 100%, respectively), while K8 was seen in 10% cases and K14 and K19 in none. In contrast, epithelioid angiosarcomas (EAs) were often positive for K8 and K18 (approximately 50%), whereas they less commonly showed K7 and only occasionally K19; all tumors were negative for K14 and with the antibody 34betaE12. Nonepithelioid angiosarcomas (AS) less commonly showed keratin expression with K7, K8, and K18 being positive in 20% of cases, and K14 and K19 in none of the cases. Epithelial membrane antigen (EMA) was occasionally detectable in EHE (2/19) but was present in 4 of 16 (25%) EAs and 17 of 48 (35%) nonepithelioid AS. These findings document the common presence of focal reactivity for K7 and K18 in subsets of normal endothelia and also the frequent presence of simple epithelial keratins in malignant vascular tumors, while such expression is uncommon in nonepithelioid angiosarcomas. K- and EMA-positivity in neoplastic endothelia needs to be considered in the evaluation of human tumors. K antibodies such as those specific to K19 or AE1 that do not react with K8 and K18 should be used in the differential diagnosis of epithelioid vascular tumors and carcinomas.
血管内皮细胞是一种特殊的、源自间充质的上皮样衬里细胞，是良性和恶性血管肿瘤的重要参与者。尽管低等动物的内皮细胞通常表达角蛋白（K），但人类内皮细胞一般为K阴性且波形蛋白阳性。然而，在一些内皮细胞和某些上皮样血管肿瘤中已观察到K表达。在本研究中，我们系统地检测了正常人类血管内皮细胞以及一系列人类血管肿瘤（每种标志物至少检测137个肿瘤）中莫尔分类目录中的简单上皮角蛋白多肽（K7、K8、K18和K19）。还使用针对K14的抗体和识别复层上皮几种角蛋白的单克隆抗体34βE12对选定的血管肿瘤进行评估。正常静脉、小静脉和淋巴管的内皮细胞通常对K7和K18呈局灶性阳性，而在所使用的抗体检测下，非肿瘤性内皮细胞中未见K8、K14和K19。淋巴管瘤（7例中的6例）和静脉血管瘤（13例中的6例）常显示K7阳性的内皮细胞；K18的检测较少见，而未检测到K8和K19。上皮样血管内皮瘤（EHE）在大多数病例中显示K7和K18表达（分别为50%和100%），而10%的病例中可见K8，K14和K19均未检测到。相比之下，上皮样血管肉瘤（EA）通常对K8和K18呈阳性（约50%），而K7阳性较少见，仅偶尔见K19阳性；所有肿瘤对K14和抗体34βE12均为阴性。非上皮样血管肉瘤（AS）较少显示角蛋白表达，K7、K8和K18在20%的病例中呈阳性，K14和K19在所有病例中均未呈阳性。上皮膜抗原（EMA）在EHE中偶尔可检测到（占19例中的2例），但在16例EA中有4例（25%）呈阳性，在48例非上皮样AS中有17例（35%）呈阳性。这些发现证明了正常内皮细胞亚群中K7和K18局灶性反应的普遍存在，以及恶性血管肿瘤中简单上皮角蛋白的频繁存在，而这种表达在非上皮样血管肉瘤中并不常见。在评估人类肿瘤时，需要考虑肿瘤性内皮细胞中的K和EMA阳性情况。在鉴别上皮样血管肿瘤和癌时，应使用不与K8和K18反应的K抗体，如对K19或AE1特异的抗体。
