PATHOLOGY Department of Veterinary Public Health and Animal Pathology, School of Veterinary Medicine, Bologna, Italy E-cadherin Expression in Canine Mammary Carcinomas with Regional Lymph Node Metastases B. Brunetti 1 , G. Sarli 1 , R. Preziosi 1 , S. Leprotti 1 and C. Benazzi 1,2 Address of authors: 1 Dipartimento di Sanita` Pubblica Veterinaria e Patologia Animale, Universita` degli Studi di Bologna, via Tolara di Sopra, 50, 40064 Ozzano Emilia (Bologna), Italy; 2 Corresponding author: E-mail: Benazzi@vet.unibo.it With 5 figures and 1 table Received for publication: April 01, 2003 Summary E-cadherin (E-cad) is a cell adhesion molecule known for its tumour invasion-suppressor function. This study investigated the immunohistochemical expression of E-cadherin in 19 cases of malignant mammary tumours of the dog and the relation- ship between E-cadherin expression in primary tumours and in regional lymph node metastases. E-cadherin expression is not always parallel in the primary tumour and in the lymph node metastasis. One year follow-up was available in 12 of 19 cases. Three different patterns of expression were revealed in the lymph node metastases compared with the primary tumour: downregulation when the protein expression was weaker in the metastasis than in the primary tumour; upregulation when E-cadherin was stronger in the lymph node than in the primary tumour, and a similarly intense expression when it was equal in the metastasis and in the tumour. The lymph node pattern revealed a prevalent upregulation or downregulation with respect to the primary tumour, whereas a similar expression of E-cadherin was encountered in less than 50% of cases. Introduction E-cadherin (E-cad) is a member of the cadherin family known to play an important role in regulating intercellular adhesion in epithelial tissues (Takeichi, 1991). E-cad is expressed on the basolateral surfaces of the epithelial cells at points of cell to cell contact (Boller et al., 1985), and has been found to suppress tumour invasiveness (Frixen et al., 1991). Tumours with partial or total loss of E-cad expression are more infiltrating, higher grade, and more likely to have spread to lymph nodes. In breast cancer, decreased levels of E-cad expression and lymph node metastases have been correlated with tumour grade (Heimann et al., 2000). A mechanism triggering the metastasis of tumour cells is the downregulation of the intercellular adhesion molecules, such as E-cad, which promote disaggregation from the primary tumour. The percentage of metastases was higher in women with breast tumours in which E-cad expression was lacking (Gamallo et al., 1993; Oka et al., 1993; Madhavan et al., 2001; Yoshida et al., 2001), emphasizing the prognostic role of E-cad reduc- tion in primary tumours. However, the evidence was contro- versial comparing primary tumours and their collector lymph node metastases (Bongiorno et al., 1995). However, lymph nodes containing metastatic cells from breast and colorectal tumours showed reduced E-cad protein expression (Dorudi et al., 1993; Oka et al., 1993; Yoshida et al., 2001) whereas E-cad was preserved in lung, oesophageal, gastric and breast cancer metastasis studies (Shimoyama et al., 1989; Bongiorno et al., 1995; Yoshida et al., 2001). An increase in E-cad protein expression was also reported in some lymph node metastases of gastric, breast and bladder cancer when compared with primary tumours (re-expression) (Mayer et al., 1993; Bukholm et al., 2000; Byrne et al., 2001). In the dog, there is only one report (Restucci et al., 1997) on E-cad expression in five cases of primary mammary tumour and the collector lymph node metastasis. In four of these cases, the expression of E-cad in the lymph nodes was similar to the primary tumour and in one case, it was upregulated. The present study was carried out on malignant metastatic tumours (all carcinomas which are more common than mesenchymal tumours) to further investigate the relationship between E-cad expression in canine mammary tumours and their lymph node metastases. Materials and Methods Cases Malignant mammary tumours with their regional lymph node metastases from 19 dogs were analysed for E-cad expression. All the dogs had undergone surgery at the University Clinic of Veterinary Surgery (Bologna, Italy) and in private clinics. None showed evidence of distant metastases in radiographic and ultrasonographic investigations performed prior to sur- gery. Tissue specimens were immediately fixed in 10% buffered formalin and routinely processed. Histological diagnoses were established on haematoxylin and eosin-stained slides and followed the WHO classification (Misdorp et al., 1999). Tumour stage was determined according to a previously proposed system (Gilbertson et al., 1983). Information in 12 of 19 cases was obtained from the referring veterinarians and animal owners by telephone contact. The information U.S. Copyright Clearance Center Code Statement: 0931–184X/2003/5010–0496 $15.00/0 www.blackwell-synergy.com J. Vet. Med. A 50, 496–500 (2003) Ó 2003 Blackwell Verlag, Berlin ISSN 0931–184X