Assessment of p53 and Ki-67 expression in snuff-induced lesions.

An immunohistochemical study of snuff-induced lesions with a monoclonal antibody (DO-7) specific to p53 mutant and wildtype antioncogene product demonstrated nuclear overexpression of the mutant protein in 45.9 nuclear profiles/mm2 epithelium (SEM 10.8; n = 15) compared with only 0.18 positively stained nuclear profiles/mm2 in the control group (SEM 0.18; n = 4). Furthermore, the biopsy material was also stained with the antibody Ki-67, which has been shown to be excellent for the estimation of the growth fraction in both normal and malignant human tissues. Ki-67 stained positive in 566.1 nuclear profiles/mm2 epithelium (SEM 85.0; n = 15) in the snuff-group compared with 20.2 nuclear profiles/mm2 (SEM 4.9; n = 4) in the control group. To the best of our knowledge, this is the first study showing overexpression of p53 protein and Ki-67 in snuff-induced lesions. The results may indicate that the p53 gene is involved in the initial events leading to subsequent malignant transformation of oral mucosa exposed to snuff. Furthermore, mutations of the p53 gene have been associated with increased cellular proliferation with greater risk of perpetuation of mutations and malignant transformation.