[57] Expression of p27 was selleckchem Temsirolimus inversely correlated with the expression of Ki-67, which has been reported to be a good indicator of cell proliferation activity in premalignant and malignant oral lesions.[60] These findings indicate that reduced expression of p27 may play an important role in an abnormal proliferation through a loss of cell cycle regulation which may concern the cancer development directly or indirectly.[61] The down-regulation of p27 is believed to play an important role in cancer invasion process, as well as metastasis mediated by loss of cell adhesion either directly or indirectly, due to heterogeneous its expression which tends to diminish toward the invasive fronts in some early invasive OSCCs.

[62] Aggressive human cancers were also found to express low levels of p27, which may be due to its decreased stability or due to an enhancement of its degradation.[63] The simultaneous involvement of cyclin-D1 and p27 genes was estimated by Pignataro et al., and an inverse correlation between p27 and cyclin D1 expression was established. It was concluded that the absence of p27 expression may be due to sequestration by cyclin D1 and that the balance of these two opposing regulators of the cell cycle may be a determinant factor in cell proliferation.[64] Similar results were obtained in our study where p27 expression was inversely related to that of cyclin-D1 owing to their functional diversity. The other marker of interest in our study is p63, a homologue of the p53 gene which is located on chromosome 3q27-29.

A dual role of p63 protein has been reported; during embryogenesis, p63 may be the molecular switch required for initiation of epithelial stratification because, if lacking p63, epithelium remains single layered; for mature epithelium, p63 needs to be switched off for terminal differentiation to take place; otherwise, p63 may maintain the proliferative potential of basal keratinocytes preventing stratification to occur. Based on immunohistochemical data, p63 protein is expressed in the proliferative layer of cells near the basement membrane of the normal oral mucosa, where it likely serves to prevent basal cells from differentiating and thereby helps to maintain their basal cell status.[29] Although, p63 gene has extensively been studied in various tumors, only some have examined p63 expression in oral squamous cell carcinoma, but the involvement of p63 in human oral potentially malignant disorders remains largely unelaborated except for a few studies.

Earlier studies have reported the expression of the p63 protein and mRNA in oral epithelial dysplasia,[65] however; no attempt was made to grade degree of staining with respect to the severity of the dysplastic lesions. But later the relationship between p63 protein expression and various grades Drug_discovery of oral epithelial dysplasia was also analyzed.