001), from mild to severe dysplasia, which is similar to the results of the previous studies. Normally, upon the maturation of the oral stratified squamous epithelium, the expression of p63 protein should have been downregulated and p63 protein has rarely been detected in superficial layers of the normal epithelium.[29] else However, upon dysplastic change, dysplastic keratinocytes above the basal layers may shift to a status similar to the embryogenesis condition that are still able to express p63 protein producing an anti-differentiation effect, as well as maintain the proliferative capacity of dysplastic cells in oral dysplastic mucosa.[29] Furthermore, the increased proliferating cell population in both basal and suprabasal layers of epithelial dysplasia suggest that proliferating cells might increase not only in a superficial direction but also downward to the basal layer in epithelial dysplasias.

[30] Although, previous studies have described increase in the total number of proliferating cells according to the degree of epithelial dysplasia and SCC, the increased expression of p63 in the suprabasal layer may be a useful marker of high-grade dysplasia.[67] It was suggested that p63 may contribute to the development of epithelial dysplasia through the alteration of stem cell function in the basal layer, resulting in an increased number of proliferating cells, and its altered distribution in basal and suprabasal layers within oral epithelial dysplasia.[39] According to Steeg and Abrams (1997),[68] for a new prognostic marker to enter into routine clinical use, at least three criteria must be met.

(1) The marker provides information independent of any better than conventional pathological criteria. (2) The marker provides information that can alter treatment decisions. (3) Studies with the marker are reproducible. Many reports have validated the utility of p27, cyclin D1 and p63 as prognostic and/or diagnostic markers,[69] hence these markers can prove to be valuable aids in the grading of oral epithelial dysplasia. Markers of cell proliferation have been used to predict prognosis and progression to malignancy in cases where clinical and pathological parameters fail to determine its aggressiveness[70] and the evaluation of the cell growth fraction is considered to be potentially one of the most powerful tools for predicting neoplastic behavior. The assessment of cell proliferation activity by immunohistochemistry has been extensively studied in Carfilzomib order to find new prognostic markers for a wide variety of tumors.[71,14] Many authors have stated that one of the important characteristics of the neoplastic transformation of a steady-state epithelial system is the alteration of growth rate, commonly reflected as increased cell proliferation.