p53 inactivation in chewing tobacco-induced oral cancers and leukoplakias from India

The inactivation of p53 tumour suppressor gene vis-a-vis point mutation, ov erexpression and degradation due to Human Papilloma virus (HPV) 16/18 infec tion, was examined in chewing tobacco-associated oral cancers and oral leuk oplakias from India. The analysis of mutations was assessed by polymerase c hain reaction (PCR) with single strand conformation polymorphism (PCR-SSCP) of exons 5-9 on DNA from 83 oral cancer cases, and the mutations confirmed by direct nucleotide sequencing of the PCR products. p53 protein expressio n was evaluated by immunohistochemical analysis on paraffin-embedded sectio ns of 62 representative oral cancer biopsies and 22 leukoplakias, using p53 -specific monoclonal antibody DO-7. The presence of HPV16/18 was detected i n the 83 oral cancer cases by PCR analysis using HPV L1 consensus sequences , followed by Southern hybridization with type-specific oligonucleotide pro bes. Forty-six per cent (38/83) of oral cancer tumours showed p53 alteratio ns, with 17% (14/83) showing point mutations, 37% (23/62) with overexpressi on and 25% (21/83) with presence of HPV16 wherein the E6 HPV16 protein degr ades p53. HPV18 was not detected in any of the samples. Ninety-two per cent concordance was observed between missense point mutations and overexpressi on of p53 protein. A significant correlation was not observed between p53 a lterations in oral cancer and clinico-pathological profile of the patients. Twenty-seven per cent (6/22) of oral leukoplakias showed p53 overexpressio n. The overall p53 alterations in oral cancer tissues and oral lesions are comparable to data from the oral cancers reported in the Western countries with smoking and alcohol-associated oral cancers, and suggest a critical ro le for p53 gene in a significant proportion of oral cancers from India. The overexpression of p53 protein in leukoplakias may serve as a valuable biom arker for identifying individuals at high risk of transformation to maligna nt phenotype. (C) 1999 Elsevier Science Ltd. All rights reserved.