A high prevalence of p53 mutations in pre-malignant oral erythroplakia

Oral squamous-cell carcinoma is thought to be preceded by a number of precu rsor stages which induce morphological changes in cells of the oval mucosa resulting in clinically detectable pre-malignant lesions such as erythropla kia or leukoplakia. To better understand the etiology of oral erythroplakia , we have examined the p53 tumor-suppressor gene (exons 5-9) for mutations in 24 oral erythroplakia lesions of varying dysplastic phenotypes by PCR/si ngle-strand conformational polymorphism and direct DNA-sequencing analyses. A total of IZ p53 mutations were detected in II of 24 (46%) erythroplakia specimens (one specimen contained two different p53 mutations); 25% were si ngle-base-pair deletions and 33% were either G:C--> T:A transversions or G: C--> A:T transitions. A high prevalence of p53 mutation was observed in all categories of erythroplakia lesions: 33% for mildly dysplastic lesions, 50 % for lesions exhibiting moderate to severe dysplasia and 50% for lesions t hat were carcinoma in situ. Although the combined prevalence of p53 mutatio ns observed in erythroplakia was significantly higher (p = 0.02) than that observed earlier for leukoplakia, the prevalence of p53 mutations was simil ar in erythroplakia and leukoplakia specimens from smokers. The prevalence and spectrum of p53 mutations observed in this series of erythroplakia lesi ons are similar to those observed for oral squamous-cell carcinoma. These r esults indicate that mutations of the p53 gene may be linked to the high ma lignant potential of erythroplakia and provide further evidence that p53 mu tation may be an early event in the genesis of oral squamous-cell carcinoma . (C) 1999 Wiley-Liss, Inc.