Association of p53 gene mutation and telomerase activity in resectable non-small cell lung cancer

Purpose: Mutation of the p53 gene and deregulation of telomerase may be ess ential for canceration in some malignant diseases. However, relationships b etween these occurrences have not yet been clarified. We examined the roles of p53 gene mutation and telomerase activity relative to the clinical and pathologic features of non-small cell lung carcinoma (NSCLC). Methods: Frozen sections of 40 surgically resected NSCLC specimens were use d. DNA extracted from fresh tumor specimens was analyzed with polymerase ch ain reaction (PCR), single-strand conformation polymorphism (SSCP) method, to screen alterations in the p53 gene. Exons showing aberrant band shifts o n SSCP were reamplified, and the PCR products were directly sequenced. In a ddition, the telomerase activity of the same specimens was analyzed quantit atively with the fluorescence-based telomeric repeat amplification protocol assay, and the total product generated (TPG) method. Clinical and patholog ic parameters were evaluated using a statistical analysis system. Results: Mutations of the p53 gene relevant to an altered protein were conf irmed in 19 of 40 specimens (47.5%). The TPG of 40 specimens was 75.24 +/- 15.55 (mean +/- SE). The TPG of the 19 specimens positive for p53 gene muta tion was significantly higher than that of the 21 specimens negative for p5 3 gene mutation. Furthermore, the degree of cell differentiation was signif icantly correlated with both p53 gene mutation and high telomerase activity . Conclusions: p53 gene mutation and high telomerase activity cooperate to in duce tumorigenesis and low-grade differentiation in NSCLC. Simultaneous occ urrence of p53 gene mutation and high telomerase activity may be relevant t o the grade of malignancy in NSCLC.