Expression of p16, p53 and Ki-67 proteins in the progression of epithelial dysplasia of the oral cavity.

Abstract. Background: The overexpression of the protein
products of genes associated with the cell cycle tumour
protein53 (p53), cyclin-dependent kinase inhibitor 2A (p16)
and antigen identified by monoclonal antibody Ki-67 (Ki-67)
is apparently of great significance. This study evaluated the
immunohistochemical expression of these proteins in
precancerous lesions and in carcinoma of the oral cavity.
Materials and Methods: The nuclear expression of p53 and Ki-
67 and nuclear and/or cytoplasmic expression of p16 protein
was examined in 54 biopsy specimens from the oral cavity
obtained over a period of 3 years. The samples included 18
cases of normal/hyperplastic mucosa, 25 cases of dysplasia
and 11 cases of invasive squamous cell carcinoma. The
specimens were grouped into three categories: 1 = no or mild
dysplasia, 2 = moderate or severe dysplasia, and 3 = invasive
carcinoma. Results: p16 was negative in all the group 1
specimens, while both p53 and Ki-67, when present, were
limited to the cells of the basal layer. In the group 2
specimens, the number of p16-, p53-, and Ki-67-positive cells
increased as the grade of dysplasia progressed. In group 3
(invasive carcinomas), p53 and p16 expression occurred
respectively in 81.8% and 54.5% of cases, while Ki-67 was
elevated in all the cases. Conclusion: The expression of the
cell-cycle proteins p16 and p53 in the dysplastic epithelium,
in association with Ki-67, may represent significant markers to
recognize evolution of precancerous disease in the oral cavity
and to improve identification of the degree of dysplasia.