Claudin-7 protein differentiates canine cholangiocarcinoma from hepatocellular carcinoma.

UNLABELLED: The aim of the present study was to characterise the expression pattern of claudin-7 tight junction protein in canine normal liver, hyperplastic and primary neoplastic lesions of the canine liver and whether this tight junction protein can help differentiate canine cholangiocarcinomas from canine hepatocellular carcinomas. METHODS AND RESULTS: Necropsy samples included 15 canine normal liver tissue samples, 10 hepatocellular nodular hyperplasias, 6 hepatocellular adenomas, 15 well-differentiated and 6 poorly differentiated hepatocellular carcinomas, 6 cholangiocellular hyperplasias, 10 cholangiocellular adenomas, 15 well-differentiated and 6 poorly differentiated cholangiocarcinomas, 6 normal extrahepatic bile ducts, 8 normal gall bladder tissue samples, and 5 cystic mucinous hyperplasias of the gall bladder. In all canine normal liver tissue samples the hepatocytes were negative for claudin-7 and the normal biliary epithelial cells showed intense basolateral membrane claudin-7 positivity. In all cholangiocellular hyperplasia samples and in all cholangiocellular adenoma samples the benign cholangiocytes showed intense basolateral membrane positivity for claudin-7. In all samples of the well-differentiated and poorly differentiated cholangiocarcinomas, the malignant neoplastic biliary epithelial cells showed intense basolateral membrane positivity for claudin-7. Neither the hyperplastic nodules of the liver cells nor the hepatocellular adenomas reacted with claudin-7. The well-differentiated and poorly differentiated hepatocellular cancers were negative for claudin-7. The epithelial cells of canine normal extrahepatic bile ducts, gall bladder and cystic mucinous hyperplasias of the gall bladder showed intense basolateral membrane positivity for claudin-7. Differences in the intensity of claudin-7 reaction were not apparent among different types of proliferative lesions of cholangiocytes or degrees of cellular differentiation of neoplastic biliary epithelial cells. CONCLUSION: Consequently, we hypothesize that claudin-7 is an excellent immunohistochemical marker of the cholangiocellular differentiation in canines and can be used to detect benign and malignant proliferative lesions of the canine biliary tract. It can also help to differentiate canine cholangiocarcinomas from hepatocellular carcinomas.

Expression of claudin-1, -2, -3, -4, -5 and -7 proteins in benign and malignant canine mammary gland epithelial tumours.

Claudins are tight junction proteins expressed by epithelial and endothelial cells. The present study has evaluated the expression of claudin-1, -2, -3, -4, -5 and -7 in 115 hyperplastic and neoplastic lesions of the canine mammary gland and compared this expression with that of normal mammary epithelium. The lesions studied included lobular hyperplasia (n=15), simple adenoma (n=20), non-infiltrating carcinoma in situ (n=20) and infiltrating carcinomas of histological grades I, II and III (n=20 of each). There was strong expression of claudin-1, -3, -4, -5 and -7 by epithelia within examples of lobular hyperplasia and simple adenoma, and strong expression of claudin-3 and -4 by non-infiltrating carcinomas and all three grades of infiltrating carcinoma. By contrast, there was reduced expression of claudin-5 and -7 by non-infiltrating and infiltrating carcinomas and the expression of these two molecules was inversely correlated with histological grade. Claudin-1 was expressed focally within carcinoma in situ, but this molecule was not detected in any invasive carcinoma. Claudin-2 was weakly expressed within areas of lobular hyperplasia and by simple adenomas, but was not expressed by any carcinoma cells. These results suggest that loss or reduction of expression of claudin-1, -2, -5 and -7 may lead to cellular disorientation, detachment and invasion in canine mammary neoplasia.