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

OBJECTIVES: (1) To determine whether the protein of the suppressor gene 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 archival tissue specimens. SETTING: The University Hospital, a tertiary referral hospital affiliated with the Oklahoma University Medical Center, Oklahoma City, Oklahoma. PATIENTS: In the first part of the study, biopsy specimens of leukoplakia from 12 persons who used snuff were compared 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 archival paraffin-embedded specimens from oral leukoplakia and correlated with the degree of epithelial dysplasia. METHODS: Accumulation of p53 protein was assessed by immunoperoxidase staining with four different primary antibodies. Positive cells were counted in five consecutive high-power fields. RESULTS: In part one, the average number of positive 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 two, the average number of positive cells was higher in the moderately dysplastic (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 the number of cells positive is strong (Spearman's correlation coefficient = 0.853). CONCLUSIONS: The accumulation of p53 protein in leukoplakia of snuff-users is higher than in normal-appearing oral mucosa from both snuff-users and nontobacco-using controls. A strong correlation exists between the degree of epithelial dysplasia present in oral leukoplakia and the number of cells staining positive for p53. The accumulation of p53 protein holds potential as an intermediate end point in studies of chemoprevention of oral cancer.