Validation of the use of proliferation markers in canine neoplastic and non‐neoplastic tissues: comparison of KI‐67 and proliferating cell nuclear antigen (PCNA) expression versus in vivo bromodeoxyuridine labelling by immunohistochemistry

Abstract

In order to evaluate the suitability of Ki-67 and proliferating cell nuclear antigen (PCNA) for determination of proliferative activity, the immunohistochemically determined nuclear expression of these antigens in canine non-neoplastic and neoplastic tissues was compared with the results of in vivo bromodeoxyuridine (BrdU) labelling, which - by measurement of the fraction of S-phase cells - is considered as the standard in the analysis of proliferative activity. The samples investigated consisted of non-neoplastic mammary and lymphoid tissues, and of benign and malignant (primary/metastatic) mammary tumours, and malignant lymphomas. Great regional heterogeneity prevented determination of an overall labelling index (LI) in normal lymphoid tissues. In the remaining combined group of samples, LI values were significantly ranked in the order PCNA>Ki-67>BrdU. However, the correlation of Ki-67 or PCNA as compared to BrdU LI values was only moderate in the combined group [approximately 0.5, Spearman rank test] as well as in most subgroups, whilst it was very poor in the group of primary mammary cancers. These observations indicate that Ki-67 or PCNA LIs as markers of proliferation do not evenly match in vivo BrdU labelling.

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.…”

Immunohistochemical Expression of Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor Associated with Tumor Cell Proliferation in Canine Cutaneous Squamous Cell Carcinomas and Trichoepitheliomas

“…16,25,28,30,31,37,38,44 Ki-67 expression is a useful prognostic indicator in canine mast cell and mammary tumors. 30,38 In canine lung cancer, adenosquamous and squamous cell carcinomas differed from the other histologic types in having significantly higher proliferation indices.…”

Regional differences of proliferation activity in the spinal cord ependyma of adult rats

“…As we expected, the number of Ki-67 positive cells significantly exceeded the amount of BrdU positive cells, which may result from the different nature of these markers. While Ki-67 is a nuclear protein naturally occurring in cells with a potential to divide and is present in all phases of the cell cycle except the phase G0 and the beginning of the G1 phase [30], BrdU only labels cells undergoing DNA synthesis [31]. Indeed, occurrence of BrdU-labeled cells in the CC region in our experiment was very rare in all investigated sections, which was also previously demonstrated using a multiple BrdU labeling in cervical, thoracic and lumbar spinal cord [9].…”