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, -3, -4, -5 and -7 proteins in low grade colorectal carcinoma of canines.

UNLABELLED: The aim of the present study was to characterise the expression pattern of claudin-1, -3, -4, -5 and -7 tight junction proteins in canine normal colorectum and in the low-grade, tubulopapillary colorectal carcinoma in canines. METHODS AND RESULTS: The biopsy samples included 10 canine normal colorectal tissues and 20 canine low grade colorectal carcinomas (CLGCCs). The canine normal colorectal mucosa was negative for claudin-1. Claudin-1 was detected as a non-diffuse intense membrane labelling of neoplastic epithelial cells in low grade colorectal cancer in canines. Fifty five per cent of all tumours showed a weak cytoplasmic pattern of staining for claudin-1 protein. The normal colorectal mucosa showed diffuse punctate positivity for claudin-3. Claudin-3 was detected as an intense lateral membrane labelling of tumour cells in CLGCCs. Claudin-4 expression in surface and crypt epithelial cells of the intact colorectal mucosa in canines was punctate. Claudin-4 molecule was detected as a lateral membrane labelling of neoplastic cells in CLGCCs. The epithelium of the CLGCCs and the low grade colorectal carcinoma were negative for claudin-5. The surface and crypt epithelial cells of the canine normal colorectal mucosa showed a diffuse lateral membranous pattern of staining for claudin-7. Claudin-7 molecule was detected as an intense membrane labelling of neoplastic cells in CLGCCs. Seventy per cent of all tumours showed weak cytoplasmic positivity for claudin-7. CONCLUSION: Consequently, we hypothesize that claudin-1 plays a role in the progression of CLGCCs. Further functional studies are needed to clarify the biological role of the mislocalization of the claudin-1 molecule from cell membrane to the cytoplasm in CLGCCs. Lower claudin-4 expression suggests that reduced expression of claudin-4 molecule may lead to cellular disorientation, detachment and invasion of CLGCCs. Further functional studies are needed to clarify the biological role of overexpression and mislocalisation of claudin-7 in CLGCCs.