A low incidence of p53 mutations in pre‐malignant lesions of the oral cavity from non‐tobacco users

To determine the incidence of pS3 mutations in pre‐malignant lesions of the oral cavity from individuals without prior history of tobacco use, we have analyzed the conserved regions of the pS3 gene (exons 5‐9) in archival oral cavity lesion specimens obtained from patients with varied tobacco use histories, by polymerase chain reaction/single strand conformational polymorphism (PCR/SSCP) and DNA sequencing analysis. Twenty‐six lesions were analyzed from 14 patients, with multiple lesions obtained from 8 patients. Six of these patients used tobacco, (3 being cigarette smokers, 1 ex‐cigarette smoker, 1 moderate cigar smoker and 1 snuff chewer). The remaining 8 patients had no prior history of tobacco use. Thirteen of the pre‐malignant lesions exhibited severe dysplasia, 9 exhibited moderate dysplasia and 4 exhibited mild dysplasia. Four of the 26 lesions exhibited pS3 mutations, each being from a tobacco user. None of the 13 lesions from never‐tobacco users exhibited pS3 mutations. There was a significantly higher p53 mutation incidence in pre‐malignant lesions from tobacco users (including ex‐smokers) than in non‐tobacco users as well as in cigarette smokers plus snuff chewers than in non‐tobacco users. Two of the mutations were observed in lesions exhibiting severe dysplasia: I in a lesion exhibiting moderate dysplasia and I in a lesion exhibiting mild dysplasia. These data suggest that pS3 mutation may be a very early event in oral cavity tumor progression and demonstrate that pre‐malignant lesions obtained from non‐tobacco users do not exhibit pS3 mutations.