Sialyl Lewis x expression in canine malignant mammary tumours: correlation with clinicopathological features and E-Cadherin expression

BACKGROUND: Sialyl Lewis x (sLe(x)) antigen is a carbohydrate antigen that is considered not only a marker for cancer but also implicated functionally in the malignant behaviour of cancer cells. Overexpression of sLe(x )is associated with enhanced progression and metastases of many types of cancer including those of the mammary gland. Canine mammary tumours can invade and give rise to metastases via either lymphatic or blood vessels. E-Cadherin is specifically involved in epithelial cell-to-cell adhesion. In cancer, E-Cadherin underexpression is one of the alterations that characterizes the invasive phenotype and is considered an invasion/tumour suppressor gene. Partial or complete loss of E-Cadherin expression correlates with poor prognosis in canine malignant mammary cancer. The aim of this study was to analyse the sLe(x )expression in canine malignant mammary tumours and to evaluate if the presence of sLe(x )correlates with the expression of E-Cadherin and with clinicopathological features. METHODS: Fifty-three cases of canine mammary carcinomas were analysed immunohistochemically using monoclonal antibodies against sLe(x )(IgM) and E-Cadherin (IgG). The clinicopathological data were then assessed to determine whether there was a correlation with sLe(x )tumour expression. Double labelled immunofluorescence staining was performed to analyse the combined expression of sLe(x )and E-Cadherin. RESULTS: sLe(x )expression was consistently demonstrated in all cases of canine mammary carcinomas with different levels of expression. We found a significant relationship between the levels of sLe(x )expression and the presence of lymph node metastases. We also demonstrated that when E-Cadherin expression was increased sLe(x )was reduced and vice-versa. The combined analysis of both adhesion molecules revealed an inverse relationship. CONCLUSION: In the present study we demonstrate the importance of sLe(x )in the malignant phenotype of canine malignant mammary tumours. Our results support the use of sLe(x )as a prognostic tumour marker in canine mammary carcinomas. Furthermore, we showed that sLe(x )and E-Cadherin expression were inversely correlated. Future studies are warranted to clarify the molecular mechanism underlying the relation between sLe(x )and E-Cadherin in canine mammary carcinoma cells which represents an important comparative model to woman breast cancer.