No abstract

Abstract. The aim of this study was to investigate the correlation between the histologic invasiveness (histologic stage) and various cell proliferation activity assays (quantity of argyrophil proteins associated with nucleolar organizer regions [AgNORs], mitotic activity, MIB1 [Ki67] immunohistochemical detection) for predicting the biologic behavior of malignant canine mammary tumors. Sixty specimens from malignant canine mammary tumors with no distant metastases (M0) at surgery were selected, and follow-up data were collected over a 2-year period. The histologic invasiveness was graded by histologic stage (stage 0 ϭ tumors without stromal invasion; stage I ϭ tumors with stromal invasion; stage II ϭ tumors with neoplastic emboli in vessels), and the proliferative indices were expressed as MIB1 index (the percentage of nuclear area immunohistochemically stained by MIB1 antibody), mitotic index (the number of mitoses per 1,000 neoplastic cells), and AgNOR index (the ratio between mean AgNOR area of tumor cells and the mean AgNOR area of fibroblasts/lymphocytes). The measures of proliferative activity were compared among groups with different histologic stages, and the influence of different prognostic variables (histologic stage, AgNOR index, mitotic index, MIB1 index) on survival time was evaluated. A significant difference in the proliferation patterns was recorded between the different histologic stages for the mitotic index (P ϭ 0.0006) and MIB1 index (0.0013). Among the different parameters considered, histologic stage (P Ͻ 0.05), AgNOR index (P ϭ 0.0291), and MIB1 index (P ϭ 0.014) revealed a significant association with prognosis in univariate analysis. AgNOR index for 1-year survival and histologic stage for 2-year survival were the most significant parameters influencing survival, as determined by multiple nonlinear logistic regression.Mammary tumors are very common in the female dog, and their malignant counterparts account for 40-50% of all histologically diagnosed neoplasms. 18 Histopathologic and clinical aspects of these tumors have been widely reviewed; [3][4][5]18,24 nevertheless, the presence of considerable variations in the biologic behavior, even among histologically malignant tumors, often does not allow an accurate prognosis using microscopic examination alone.In previous years, many efforts have been made to find correlations among clinical staging, different histomorphologic criteria, and clinical prognosis. 3,4,11,12,14,18,19,24 Unfortunately, no reliable criteria have been established, although tumor size and histologic staging or invasiveness seem to have a high prognostic value. 4,12,18,22 Assessment of cell proliferation has been useful for the evaluation of biologic behavior and potential malignancy of tumors. 15,29,32 In veterinary oncology, the recent introduction of methods applicable to formalin-fixed, paraffin-embedded tissues (Ki67 and proliferating cell nuclear antigen [PCNA] quantitation of argyrophil proteins associated with nucleolar organizer regions [AgNORs]) has allow...

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.

No abstract

No abstract