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.