P53 AND RETINOID CHEMOPREVENTION OF ORAL CARCINOGENESIS

We studied p53 protein's pattern of expression, association with retin oid response or resistance, and modulation by retinoid intervention in oral premalignancy. These p53 analyses were included in a prospective trial of the retinoid isotretinoin (1.5 mg/kg/day for 3 months) in 40 patients (45 oral premalignant lesions), Seven nonsmoking subjects (e ight oral biopsies) were included as a control, Protein levels of p53 were determined separately for the whole epithelium and the basal, par abasal, and superficial layers, A wide range of accumulated p53 protei n levels occurred in 40 (89%) of 45 lesions in basal and parabasal but not superficial layers, No p53 protein was detected in any normal con trols, Accumulation of p53 increased in direct association with histol ogical grade (P = 0.0004), An inverse relationship occurred between th e levels of accumulated p53 protein and response to isotretinoin (P = 0.006). High-dose isotretinoin did not modulate accumulated p53 protei n expression.