Carcinomas em tumores mistos mamários caninos: expressão de versican e sua relação com invasão do estroma e com grau de diferenciação mioepitelial

Abstract

Components of the extracellular matrix have been studied with the attempt to elucidate mechanisms involved in the biological behavior of tumors. Among them, the proteoglycan versican deserves highlight. Its presence has been strongly associated to cancer development, cellular differentiation and progression. Carcinomas in benign mixed tumors (CBMT) are the most common malignant tumor in female dogs and may serve as a model for studies on tumor progression. The aim of this work was to evaluate the expression of versican in in situ and invasive carcinomatous areas of CBMT, verifying possible associations with other classic prognostic factors and overall survival. Furthermore, to evaluate the expression of versican, and the relation of versican with the expression of p63, smooth muscle -actin (-SMA), proteoglycan sulfate and mucopolysaccharides in myoepithelial cells in their different differentiation stages. Clinical staging, histological grade, Nottingham Prognostic Index (NPI), immunohistochemical staining for versican, E-cadherin, Ki-67 and confirmation of invasion areas with staining for p63 and -SMA were performed on 49 cases of CBMT for the first proposal. Versican, p63 and -SMA (immunohistochemical) and proteoglycan sulfate and mucopolysaccharides (histochemical) expression were analyzed in 39 eligible cases for the second proposal. Evaluation of double staning for p63 and -SMA indicated that myoepithelial cells still found in carcinomas with invasion areas presented weak or loss of staining of at least one marker. Versican immunoreactivity was less intense adjacent to in situ carcinomatous regions when compared to invasive regions in which staining was found as more extensive areas with strong expression (p < 0.0001). Evaluation of myoepithelial cells in benign areas demonstrated significant differences between the expression of versican and -SMA in normal (p < 0.0001), polygonal (p < 0.0001) and stellate-shaped (p = 0.0013) myoepithelial cells, as well as in the myxoid (p < 0.0001) and immature chondroid (p < 0.0001) matrix. Furthermore, differences were also observed between p63 reactivity and versican in spindle-shaped myoepithelial cells (p = 0.0029), myxoid (p = 0.0174) and immature chondroid areas (p = 0.0156). These results suggest that, as the myoepithelium gains mesenchymal characteristics, a decrease in p63 and -SMA molecule expression and increase in versican expression occurs. In addition direct relation between versican and invasion suggests the role of this molecule in tumor progression.