Expression of the claudin-4 molecule in benign and malignant canine hepatoid gland tumours.

Claudins are integral membrane proteins of the tight junction structures expressed by epithelial and endothelial cells. The present study has evaluated the expression of claudin-4 in 10 normal canine hepatoid glands and in 67 hepatoid glands with hyperplastic and neoplastic lesions. The lesions studied included normal hepatoid glands (n = 10), nodular hyperplasias (n = 10), adenomas (n = 12), epitheliomas (n = 15), differentiated carcinomas (n = 15) and anaplastic carcinomas (n = 15). There was an intensive expression of claudin-4 in normal canine hepatoid glands as well as in hyperplasias and adenomas. Claudin-4 was detected as a well-localised linear circumferential membranous staining pattern of epithelial cells (mature hepatoid cells) in normal hepatoid glands, perianal gland hyperplasias and adenomas. In nodular hyperplasia and adenoma, the reserve cells showed membrane positivity for the claudin-4 molecule. There was a weaker expression in hepatoid gland epitheliomas. In the epitheliomas, the basaloid reserve cells never expressed the claudin-4 molecule. The multiple small parts of epitheliomas in which the cells exhibited typical hepatoid features showed a well-localised linear circumferential membranous staining pattern for claudin-4. The numerical score for cellular expression of claudin-4 was higher in differentiated carcinomas than in epitheliomas, but moderately lower than in adenomas. The anaplastic, poorly differentiated hepatoid gland carcinomas showed an overexpression of claudin-4. These results suggest that low claudin-4 expression in epitheliomas is a molecular characteristic indicative of increasing cellular disorientation, detachment motility and invasion by tumour cells, and claudin-4 seems to be helpful in distinguishing undifferentiated carcinomas from differentiated carcinomas and epitheliomas of the hepatoid gland. In addition, claudin-4 can help distinguish epithelioma from differentiated carcinoma of the canine hepatoid gland.