Brunetti B, Sarli G, Preziosi R, Monari I, Benazzi C
Department of Veterinary Public Health and Animal Pathology, Division of Veterinary Pathology, via Tolara di Sopra 50-40064, Ozzano Emilia, Bologna, Italy.
Vet Pathol. 2005 Nov;42(6):781-7. doi: 10.1354/vp.42-6-781.
E-Cadherin and beta-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 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 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, beta-cat, and E-cad/beta-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; beta-cat, P = 0.29; E-cad/beta-cat P = 0.36). Grouping cases for histologic invasiveness, the expression of E-cad or beta-cat and E-cad/beta-cat showed a progressive reduction that paralleled an increase in invasiveness from noninfiltrating to stage-II tumors (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 analysis of variance between the cases grouped for preserved or reduced E-cad, beta-cat, and E-cad/beta-cat variables. In conclusion, reduced expression of E-cad, beta-cat, or E-cad/beta-cat was significantly associated with the progression from noninfiltrating to highly infiltrating tumors but not with proliferation or survival.
E-钙黏蛋白和β-连环蛋白在肿瘤侵袭中发挥作用,且这两种蛋白也对肿瘤增殖产生影响。本研究以犬乳腺肿瘤为对象,旨在分析单独免疫组化评估以及联合评估(E-钙黏蛋白/β-连环蛋白)的E-钙黏蛋白(E-cad)和β-连环蛋白(β-cat)对生存的影响及其与几种增殖指数(银染核仁组织区[AgNOR]指数、MIB1指数、有丝分裂指数)的关系。对60例福尔马林固定、石蜡包埋的犬乳腺恶性肿瘤标本进行免疫组化。当在超过75%的细胞膜上普遍存在且其他表达形式(即膜表达少于75%、细胞质表达和阴性表达)减少时,标记被定义为保留。60例病例中,E-cad、β-cat和E-cad/β-cat分别有22例、12例和11例保留。同一肿瘤中两种蛋白的免疫组化表达显著相关(P = 0.0001;R = 0.57)。生存分析显示,保留组与减少组相比,结果无差异(E-cad,P = 0.31;β-cat,P = 0.29;E-cad/β-cat,P = 0.36)。按组织学侵袭性对病例进行分组,E-cad或β-cat以及E-cad/β-cat的表达呈逐渐降低,这与从非浸润性肿瘤到II期肿瘤侵袭性增加平行(E-cad,P < 0.001;β-cat,P < 0.05;E-cad/β-cat,P < 0.05)。通过方差分析比较E-cad、β-cat和E-cad/β-cat变量保留或减少分组病例的有丝分裂指数、MIB 1指数和AgNOR指数,未获得显著差异。总之,E-cad、β-cat或E-cad/β-cat表达减少与从非浸润性肿瘤进展为高度浸润性肿瘤显著相关,但与增殖或生存无关。