Claudin-5: A Novel, Highly Sensitive and Specific Endothelial Marker.
Wonwoo Shon, Laurie A Popp, Andrew L Folpe. Mayo Clinic, Rochester, MN
Background: Claudin-5, a member of the claudin family of tight junction-associated proteins, is thought to be chiefly expressed in endothelial cells under normal states. Although claudin-5 expression has been recently observed in rare cases of carcinoma of pancreatic and lung origin, antibodies to claudin-5 have not been systematically examined as diagnostic reagents. Prompted by a recent study showing claudin-5 expression in canine angiosarcomas, we studied claudin-5 expression in angiosarcomas, non-endothelial mesenchymal tumors, carcinomas, and normal tissues.
Design: Formalin-fixed, paraffin embedded whole sections (20 angiosarcomas, 1 epithelioid hemangioendothelioma, 39 non-endothelial mesenchymal tumors, 2 mesotheliomas, 2 melanomas, 11 carcinomas of various sites, and 2 germ cell tumors) and 2 tissue microarray sections (1 with 146 pancreatic adenocarcinomas; 1 with 42 cases each of lung, ovarian, and pancreatic carcinoma as well as normal tissues) were immunostained for claudin-5 (polyclonal, 1:100, Abcam) using heat-induced epitope retrieval and the Dako EnVision detection system. Membranous immunoreactivity was scored as negative (<5%), 1+ (5-25%), 2+ (26-50%), 3+ (>51%). Appropriate controls were employed.
Results: Claudin-5 expression was seen in 19/20 (95%) angiosarcomas (1+: 5, 3+: 14) and in the case of epithelioid hemangioendothelioma (2+). All non-endothelial mesenchymal tumors were claudin-5 negative. Amongst non-mesenchymal tumors, claudin-5 expression was seen only in carcinomas of pancreatic (11/146, 8%) and gastric (2/2, 100%) origin, and in a case of yolk sac tumor. In normal tissues, claudin-5 expression was confined to endothelial cells, gastric foveolar cells, colonic surface mucosa, and placental trophoblast. The overall sensitivity and specificity of claudin-5 expression for endothelial neoplasms was 95% and 93%, respectively. Claudin-5 immunostaining was notably "clean", with little or no non-membranous positivity.
Conclusions: The sensitivity and specificity of claudin-5 immunohistochemistry for those endothelial neoplasms tested to date (primarily angiosarcoma) rivals or exceeds those of established endothelial markers (e.g., CD31, CD34, Fli-1, vWF). On-going study of additional malignant, borderline and benign vascular tumors and malformations, as well as additional non-endothelial tumors, should further clarify potential diagnostic roles for this novel endothelial marker. We have also confirmed prior reports of claudin-5 expression in a subset of pancreatic adenocarcinomas, a finding that may be potentially of value in the distinction of such tumors from carcinomas of other primary sites.
Category: Bone & Soft Tissue
Monday, February 28, 2011 11:45 AM
Platform Session: Section F, Monday Morning