Prognostic Value of Histologic Stage and Proliferative Activity in Canine Malignant Mammary Tumors

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...

Mitotic Index Is Predictive for Survival for Canine Cutaneous Mast Cell Tumors

“…3,20 In veterinary medicine, MI has been found to be predictive for outcome in canine soft-tissue sarcomas, mammary tumors, as well as cutaneous melanoma. 16,26,29 Last, it has been shown that MI strongly correlates with other parameters used to assess cell proliferation in canine and feline solid tumors, including AgNOR, MIB1, and PCNA. 25 On the basis of the fact that a variety of proliferation indices have been shown to have some prognostic value for canine MCTs, we predicted that MI would be a relatively simple, straightforward measure of proliferation that would provide similar prognostic information.…”

“…It has been demonstrated that MI is a strong predictor of outcome for a variety of human and canine cancers, including thyroid carcinoma, breast carcinoma, sarcomas, among others. 3,16,26,32 Therefore, the purpose of the following study was to determine whether MI is a useful predictor of the biologic behavior of canine MCTs, as this would provide a relatively simple method for assessing MCTs during routine histopathologic examination.…”

Immunohistochemical detection of tumour cell proliferation and intratumoural microvessel density in canine malignant mammary tumours

“…PI scores of simple solid carcinomas were higher than the other carcinomas (23). On the contrary, in another study (32), PI scores of simple tubulopapillary carcinomas were found to be higher than those of solid carcinomas, yet with complex carcinomas showing the highest PI values.…”

“…Prognostic factors can be defined as specific clinical, pathological, and biological characteristics of individuals and their tumours that permit prediction of clinical outcome and survival of patients without subjecting them to additional and adjuvant therapies after initial surgery (1). The study of prognostic factors is of utmost importance, as it enables prediction of the behaviour and clinical outcome of mammary tumours using individualised therapeutic protocols with appropriate intensity and effectiveness (11,23).…”

“…Veterinary oncologists seek information concerning the histological variant of the tumour and other prognostic indicators. Proliferative activity of tumour cells, known as proliferation index (PI) (30) is considered as a morphological indicator of tumour aggressiveness, which is an important prognostic factor to define the criteria of histomorphological diversity in determination of outcome and therapeutic strategy (23). The immunohistochemical identification of antigens specific to dividing cells using monoclonal antibodies directed against Ki-67 offers a useful approach in the evaluation of the growth fraction (8,14).…”