E-Cadherin and β-catenin Reduction Influence Invasion but not Proliferation and Survival in Canine Malignant Mammary Tumors

Abstract

E-Cadherin and β-catenin are known for their role in tumor invasion, but both proteins also exert an influence on tumor proliferation. This study, performed on canine mammary tumors, aimed to analyze the influence of E-cadherin (E-cad) and β-catenin (β-cat), immunohistochemically assessed singly and in combination (E-cad/β-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 specimens of canine mammary malignancies. The labeling 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, β-cat, and E-cad/β-cat were preserved respectively in 22, 12, and 11 out of 60 cases. Immunohistochemical expression of the two proteins in the same tumors was significantly correlated ( P = 0.0001; R = 0.57). Survival analysis revealed no difference in outcome comparing the preserved versus reduced cases (E-cad, P = 0.31; β-cat, P = 0.29; E-cad/β-cat P = 0.36). Grouping cases for histologic invasiveness, the expression of E-cad or β-cat and E-cad/β-cat showed a progressive reduction that paralleled an increase in invasiveness from noninfiltrating to stage-II tumors (E-cad, P < 0.001; β-cat, P < 0.05; E-cad/β-cat, P < 0.05). No significant difference was obtained comparing mitotic index, MIB 1 index, and AgNOR index by analysis of variance between the cases grouped for preserved or reduced E-cad, β-cat, and E-cad/β-cat variables. In conclusion, reduced expression of E-cad, β-cat, or E-cad/β-cat was significantly associated with the progression from noninfiltrating to highly infiltrating tumors but not with proliferation or survival.