ACCUMULATION OF THE P53 TUMOR-SUPPRESSOR GENE-PRODUCT IN ORAL LEUKOPLAKIA

OBJECTIVES: (1) To determine whether the protein of the suppressor gen e p53 accumulates in leukoplakia of the oral cavity in individuals who use snuff; and (2) to determine whether a correlation exists between the accumulation of p53 protein and the degree of epithelial dysplasia present in oral leukoplakia. DESIGN: Retrospective analysis of archiv al tissue specimens. SETTING: The University Hospital, a tertiary refe rral hospital affiliated with the Oklahoma University Medical Center, Oklahoma City, Oklahoma. PATIENTS: In the first part of the study, bio psy specimens of leukoplakia from 12 persons who used snuff were compa red with specimens from uninvolved oral mucosa of the same persons and with biopsy specimens from 12 nontobacco-using persons. In the second part of the study accumulation of p53 protein was determined in 42 ar chival paraffin-embedded specimens from oral leukoplakia and correlate d with the degree of epithelial dysplasia. METHODS: Accumulation of p5 3 protein was assessed by immunoperoxidase staining with four differen t primary antibodies. Positive cells were counted in five consecutive high-power fields. RESULTS: In part one, the average number of positiv e cells in the leukoplakia of snuff-users (21.89 +/- 4.33; mean +/- SE ) was higher than that of normal-appearing mucosa (4.00 +/- 1.0; p < 0 .05) and that of nontobacco-using controls (7.00 +/- 5.04). In part tw o, the average number of positive cells was higher in the moderately d ysplastic (140.36 +/- 30.03) and severely dysplastic lesions (232.86 /- 26.85) than in the mildly dysplastic lesions (14.53 +/- 3.33; p < 0 .05). The correlation between the degree of epithelial dysplasia and t he number of cells positive is strong (Spearman's correlation coeffici ent = 0.853).CONCLUSIONS: The accumulation of p53 protein in leukoplak ia of snuff-users is higher than in normal-appearing oral mucosa from both snuff-users and nontobacco-using controls. A strong correlation e xists between the degree of epithelial dysplasia present in oral leuko plakia and the number of cells staining positive for p53. The accumula tion of p53 protein holds potential as an intermediate end point in st udies of chemoprevention of oral cancer.