MOLECULAR ANALYSIS OF P53 GENE IN LARYNGEAL PREMALIGNANT AND MALIGNANT LESIONS - P53 PROTEIN IMMUNOHISTOCHEMICAL EXPRESSION IS POSITIVELY RELATED TO PROLIFERATING CELL NUCLEAR ANTIGEN LABELING INDEX

This study was undertaken in order to investigate the molecular nature of the p53 gene in 19 laryngeal squamous cell carcinomas and dysplasi as. Moreover, we have examined the possible relationship between proli ferating cell nuclear antigen (PCNA) expression and p53 protein detect ion status in 42 laryngeal premalignant and malignant lesions in which 14 of the 19 samples used in the molecular study were included. p53 g ene analysis was performed with the single-strand conformation polymor phism technique. PCNA was stained with the peroxidase/antiperoxidase i mmunohistochemical method using the monoclonal antibody PC-10. Data fr om previous work concerning p53 expression was used. We found that 9 o f 12 of the immunohistochemically p53 positive (+) cases had mutations in exons 5 or 6. In the remaining immunohistochemically p53(+) and p5 3 negative (-) specimens there was no indication of sequence alteratio ns. Furthermore, we did not observe any deletions in the chromosomal r egion 17p31.1 which encodes exons 4-8 of the p53 gene. The PCNA labell ing index (LI) increased progressively with p53 protein detection stat us (percentage of cells immunohistochemically positive for p53). The d ifference between the group with the higher percentage of p53(+) cells and the others was statistically significant. These data show that al though there is a discrepancy between immunohistochemical demonstratio n of p53 and molecular analysis, a large proportion of the former harb ours the mutant form of the protein. In addition, p53 overexpression i s positively correlated with PCNA LI, a finding which accompanies tumo ur progression.