Immunohistochemical Detection of Ki-67 and PCNA in Canine Mammary Tumors: Relationship to Clinical and Pathologic Variables

Abstract

The objectives of this study were to measure the proliferation indices in canine mammary tumors using immunohistochemical detection of Ki-67 and proliferating cell nuclear antigen (PCNA), to determine the relationship of these antigens to clinical and pathologic variables, and to investigate the usefulness of these antigens as prognostic indicators. Ninety-six female dogs with 115 primary nonmetastasized spontaneous mammary tumors and dysplasias were included in the study. Immunostaining was performed using MIB-1 and PC10 monoclonal antibodies against Ki-67 and PCNA, respectively. Ki-67 and PCNA proliferation indices were determined. Dogs were followed for 18 months, with clinical examinations every 3-4 months. There was a significant correlation between Ki-67 and PCNA indices in the dogs with dysplasias and benign tumors but not in the dogs with malignant tumors. The clinical stage at first presentation was related to the proliferative index measured with Ki-67 but not to that measured with PCNA. Proliferation indices were significantly lower in the nonmalignant tumors and dysplasias than in the malignant tumors. In malignant tumors, the PCNA index had a positive correlation with the histologic malignant grade and the nuclear grade. High index values of Ki-67 were positively correlated with metastasis, death from neoplasia, low disease-free survival rates, and low overall survival rates. PCNA displayed no significant association with these variables. Multivariate analyses concerning metastasis, disease-free survival, and overall survival revealed that the Ki-67 index had prognostic value.

Immunohistochemical evaluation of e-cadherin, Ki-67 and PCNA in canine mammary neoplasias: correlation of prognostic factors and clinical outcome

“…More recently, other authors have tried to relate cell proliferation markers with the diagnosis, prognosis and outcome of breast neoplasms (Pena et al 1998, Zacchetti et al 2003, Kushlinskii et al 2004, Zuccari et al 2004, Nowak et al 2006. Nowak et al (2006) confirmed the relationship between Ki-67 and PCNA.…”

“…Some researchers have reported the value of these nuclear antigens in the prediction of disease-free interval and overall survival as independent prognostic factors in multivariate analyses (Takeishi 1991, Wintzer et al 1991, Veronese et al 1993, Rabenhorst et al 1994, Delahunt et al 1995, Pena et al 1998, Fitzgibbons et al 2000. Other authors have reported inconsistent results (Thomas et al 1993, Gasparini et al 1994.…”

Differences in Indicators of Malignancy Between Luminal Epithelial Cell Type and Myoepithelial Cell Type of Simple Solid Carcinoma in the Canine Mammary Gland

“…It has been previously demonstrated that infiltrative growth, vascular/lymphatic invasion, and lymph node metastasis are good criteria for indicating malignant behavior in canine mammary carcinomas. 6,8 The Ki-67 labeling index, known as an independent and objective prognostic factor in disease-free and overall survival, 8 was also higher in true SSC (mean rate: 31%; Fig. 10) compared with MM and BC (25% and 21%, respectively; SSC vs BC, P < .01).…”

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

“…The mortality rate of grade III tumours was also 7 times higher than that of grade II tumours. In another study, Pena et al (18) reported that increased Ki-67 expression was an objective prognostic parameter in predicting the postsurgical behaviour of canine mammary carcinomas, but it was not objective prognostic parameter for predicting metastases, disease free survival, and overall survival. Graham and Myers (10) stated that IMD was higher in metastatic tumours than benign tumours, but there was no significant difference between malignant tumours with and without metastases.…”