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  • Title: Claudin-5 as an immunohistochemical marker for angiosarcoma and hemangioendotheliomas.
    Author: Miettinen M, Sarlomo-Rikala M, Wang ZF.
    Journal: Am J Surg Pathol; 2011 Dec; 35(12):1848-56. PubMed ID: 21959309.
    Abstract:
    Claudin-5 is a tight junction protein expressed in endothelial cells and in some epithelial cells. It has been shown as a marker in canine angiosarcoma; however, data on human mesenchymal tumors are limited. In this study, we examined claudin-5 in selected normal tissues, in 280 benign and malignant vascular tumors, and in 448 other epithelial, mesenchymal, and neuroectodermal tumors. Early human embryos showed limited claudin-5 expression in endothelia of large truncal vessels, in liver sinusoids, and in the epidermis. In adult human tissues, claudin-5 was widely present in the endothelia of vessels of different calibers. However, neovascular capillaries in carcinomas and other tumors were often negative. Claudin-5 was also present in many glandular and ductal epithelia, hair shafts, and glomerular podocytes. Capillary and cavernous hemangiomas and lymphangiomas generally showed endothelial positivity; however, many vessels, especially those with poorly formed lumina, were negative in juvenile capillary hemangiomas, and fewer vessels were highlighted in lobular capillary hemangiomas. Hemangioendotheliomas of retiform, kaposiform, epithelioid, and epithelioid sarcoma-like types showed positivity, the latter in a diffuse cytoplasmic manner. Most angiosarcomas (115 of 119) and Kaposi sarcomas (28 of 29) showed strong labeling, but rare cases only contained positive cytoplasmic dots. Claudin-5 was commonly present in carcinomas (except in sarcomatoid ones), but most tumors showed heterogenous labeling weaker than that in angiosarcomas. Seminomas and renal cell, hepatocellular, and signet ring cell carcinomas were negative. Among non-vascular mesenchymal tumors, biphasic synovial sarcoma was the only tumor to contain claudin-5-positive nonvascular elements. In hemangiopericytomas, glomus tumor, and melanomas, claudin-5 was expressed in endothelial cells only. Claudin-5 is a promising new marker for angiosarcomas and hemangioendotheliomas, but widespread expression in carcinomas and biphasic synovial sarcoma should be considered in the differential diagnosis and addressed with the use of an antibody panel including keratins, especially the more epithelial-specific AE1/AE3 and epithelial membrane antigen.
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