MUTATED AND WILD-TYPE P53 EXPRESSION AND HPV INTEGRATION IN PROLIFERATIVE VERRUCOUS LEUKOPLAKIA AND ORAL SQUAMOUS-CELL CARCINOMA

The frequencies of overexpression and mutation in the p53 tumor suppre ssor gene were examined in proliferative verrucous leukoplakia and ora l squamous cell carcinoma with immunohistochemistry and single-strand conformation polymorphism analysis of DNA fragments amplified by polym erase chain reaction. Ten samples each of normal oral mucosa, prolifer ative verrucous leukoplakia, and squamous cell carcinoma were immunost ained with antibodies against p53 protein; 8 of 10 cases of proliferat ive verrucous leukoplakia cases and 7 of 10 cases of oral squamous cel l carcinoma were positive for p53 protein. Minimal staining was observ ed in normal oral tissues. The quantified labeling indexes demonstrate d a range that corresponded to lesion progression. Single-strand confo rmation polymorphism analysis revealed p53 gene mutations within exons 5 to 8 in 40% (4 of 10) of the squamous cell carcinoma samples. Two o f the 4 mutated squamous cell carcinoma samples lacked p53 expression. No p53 mutations were detected in proliferative verrucous leukoplakia tissues. Human papillomavirus 16 was identified in 2 of 7 p53 positiv e oral squamous cell carcinoma samples, Human papillomavirus 16 and 18 were identified in two of eight p53 positive proliferative verrucous leukoplakia samples. One p53 negative squamous cell carcinoma sample w as positive for human papillomavirus 16 and had a mutation in exon 6 o f the p53 gene. Human papillomavirus infection along with p53 expressi on plays a yet to be defined role in the pathogenesis of a limited num ber of cases of proliferative verrucous leukoplakia and squamous cell carcinoma. p53 Immunohistochemistry, p53 gene mutations, and human pap illomavirus infection prevalence do not provide a means to differentia te between leukoplakia and carcinoma and do not provide a predictive t est for progression of leukoplakia to carcinoma.