A LOW INCIDENCE OF P53 MUTATIONS IN PREMALIGNANT LESIONS OF THE ORAL CAVITY FROM NON-TOBACCO USERS

To determine the incidence of p53 mutations in premalignant lesions of the oral cavity from individuals without prior history of tobacco use , we have analyzed the conserved regions of the p53 gene (exons 5-9) i n archival oral cavity lesion specimens obtained from patients with va ried tobacco use histories, by polymerase chain reaction/single strand conformational polymorphism (PCR/SSCP) and DNA sequencing analysis. T wenty-six lesions were analyzed from 14 patients, with multiple lesion s obtained from 8 patients. Six of these patients used tobacco, (3 bei ng cigarette smokers, 1 ex-cigarette smoker, 1 moderate cigar smoker a nd 1 snuff chewer). The remaining 8 patients had no prior history of t obacco use. Thirteen of the pre-malignant lesions exhibited severe dys plasia, 9 exhibited moderate dysplasia and 4 exhibited mild dysplasia. pour of the 26 lesions exhibited p53 mutations, each being from a tob acco user. None of the 13 lesions from never-tobacco users exhibited p 53 mutations. There was a significantly higher p53 mutation incidence in pre-malignant lesions from tobacco users (including ex-smokers) tha n in non-tobacco users as well as in cigarette smokers plus snuff chew ers than in non-tobacco users. Two of the mutations were observed in l esions exhibiting severe dysplasia: 1 in a lesion exhibiting moderate dysplasia and 1 in a lesion exhibiting mild dysplasia. These data sugg est that p53 mutation may be a very early event in oral cavity tumor p rogression and demonstrate that pre-malignant lesions obtained from no n-tobacco users do not exhibit p53 mutations. (C) 1995 Wiley-Liss, Inc .