E-cadherin and beta-catenin reduction influence invasion but not proliferation and survival in canine malignant mammary tumours

E-cadherin and beta-catenin are known for their role in tumour invasion but both proteins also exert an influence on tumour proliferation. This study performed on canine mammary tumours aimed to analyse the influence of E-cadherin (E-cad) and beta-catenin (beta cat), immunohistochemically assessed singly and in combination (E-cad/beta-cat), on survival and their relationship with several proliferation indices (AgNOR index, MIB1 index, mitotic index). Immunohistochemistry was carried out on 60 formalin-fixed, paraffin wax-embedded archival specimens of canine malignant mammary tumours. The labelling was defined as “preserved” when prevalent on cell membranes of more than 75% of cells, and “reduced” in other forms of expression (i.e. membranous less than 75%, cytoplasmic and negative). E-cad, beta-cat and E-cad/beta-cat were preserved respectively in 22, 12, 11 out of 60 cases. Immunohistochemical expression of the two proteins in the same tumours was significantly correlated (P=0.0001; R=0.57). Survival analysis revealed no difference in outcome comparing the preserved vs reduced cases (E-cad P=0.31, beta-catenin P=0.29, E-cad/betacat P=0.36). Grouping cases for histological invasiveness, the expression of E-cad or beta-catenin and E-cad/beta-catenin showed a progressive reduction that paralleled an increase in invasiveness from non-infiltrating to stage II tumours (E-cad P<0.001, beta-cat P<0.05, E-cad/beta-cat P<0.05). No significant difference was obtained comparing mitotic index, MIB 1 index and AgNOR index by ANOVA between the cases grouped for preserved or reduced E-cad, beta-cat and E-cad/beta-catenin variables. In conclusion, reduced expression of E-cad, beta-cat or E-cad/beta cat was significantly associated with the progression from non-infiltrating to highly infiltrating tumours, but not with proliferation or survival.