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

Abstract

RESUMO.-[Avaliação imuno-histoquímica da e-caderina, Ki-67 e PCNA nas neoplasias mamárias caninas: correlação dos fatores prognósticos com a evolução clínica.] A e-caderina é uma molécula de adesão celular e a perda de sua expressão esta relacionada à invasão tumoral podendo indicar um prognóstico ruim nas neoplasias mamárias. A expressão dos marcadores de proliferação celular PCNA e especialmente o Ki-67, também têm mostrado forte valor prognóstico nesta classe tumoral. A expressão imuno-histoquímica destes marcadores foi relacionada com as características clinico-patológicas de 73 tumores removidos cirurgicamente de fêmeas caninas. Não houve correlação estatística entre estes marcadores E-cadherin is a cell-cell adhesion molecule and low e-cadherin expression is related to invasiveness and may indicate a bad prognosis in mammary neoplasms. The expression of cell proliferation markers PCNA and especially Ki-67, has also proved to have a strong prognostic value in this tumor class. The expression of these markers was related to the clinical-pathological characteristics of 73 surgically removed mammary tumors in female dogs by immunohistochemistry. There was no statistical correlation between these markers and death by neoplasm, survival time and disease-free interval. However, the loss of e-cadherin expression and marked Ki-67 expression (p=0.016) were considered statistically significant for the diagnosis (p=0.032). When evaluated as independent factors, there was evidence of the relationship between the loss of e-cadherin expression and high PCNA expression with changes in the body status (divided into obese, normal and cachectic) of female dogs (p=0.030); there was also evidence of the relationship between pseudopregnancy and e-cadherin alone (p=0.021) and for ulceration and PCNA alone (p=0.035). The significant correlation between the markers expression and these well known prognostic factors used individually or in combination suggests their prognostic value in canine mammary tumors.INDEX TERMS: Canine, cell proliferation marker, e-cadherin, immunohistochemistry, mammary neoplasm.Pesq. Vet. Bras. 28(4):207-215, abril 2008 Debora A.P.C. Zuccari et al. 208 e a morte por neoplasia, tempo de sobrevida e intervalo livre de doença. Entretanto, a perda da expressão da ecaderina e a forte expressão do 016) foram considerados estatisticamente significativos quando relacionados com o diagnóstico (p=0,032). Quando avaliados os fatores independentes, houve evidência de associação entre a perda de expressão da e-caderina e a alta expressão do PCNA com as mudanças no estado nutricional das cadelas (divididas em obesas, normais e caquéticas) (p=0,030); houve também evidência de associação entre a pseudociese e a expressão da e-caderina (p=0,021) e com a ulceração e a expressão do PCNA (p=0,035). A correlação significativa entre a expressão dos marcadores e estes, bem conhecidos fatores prognósticos usados individualmente ou em associação, sugere importante valor prognóstico destes marcadores nos tumores mamários cani...

Pathological and immunohistochemical studies on rare cases of primary extragenital transmissible venereal tumours in the mammary gland

“…It is present in all of the phases of the cell cycle, but its synthesis is greater in the S phase. Ki-67 is a non-histone protein with a mean life of less than one hour, which is not expressed in G 0 cells, but can be detected in the active phases of the cell cycle, G 1 , S, G 2 and mitosis (Pena et al 1998;Zuccari et al 2008). PCNA expression is more intense than that of Ki-67 probably because Ki-67 is restricted to the cell cycle, whereas, PCNA is also expressed in non-cycling cells in association with DNA repair.…”

Role of Cadherins in Cancer—A Review

“…Zuccari et al showed low expression of E-cadherin in canine mammary neoplasia and considered it as a marker of favorable prognosis. However, when cachexia and obesity in affected dogs occurred with low E-cadherin expression, an unfavorable prognosis was obvious [ 105 ]. The conflicting results suggest that more studies on this field should be done.…”

Expression of Cyclooxygenase-2 and Ki-67 in Actinic Keratosis and Cutaneous Squamous Cell Carcinoma in Dogs

“…Immunohistochemical analysis of Ki-67 expression has been widely used to evaluate proliferation index and it is a useful tool as a prognostic factor in canine mammary tumors, melanoma and cutaneous mast cell tumor [15][16][17][18]. Likewise, downregulation of Ki-67 expression in dogs with mast cell tumor has been related to a higher survival time [19].…”