Purpose: Mutation of the p53 gene and deregulation of
telomerase may be essential for canceration in some malignant diseases.
However, relationships between 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 used. DNA extracted from
fresh tumor specimens was analyzed with polymerase chain reaction
(PCR), single-strand conformation polymorphism (SSCP) method, to screen
alterations in the p53 gene. Exons showing aberrant band shifts on SSCP
were reamplified, and the PCR products were directly sequenced. In
addition, the telomerase activity of the same specimens was analyzed
quantitatively with the fluorescence-based telomeric repeat
amplification protocol assay, and the total product generated (TPG)
method. Clinical and pathologic parameters were evaluated using a
statistical analysis system.
Results: Mutations of the
p53 gene relevant to an altered protein were confirmed 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
mutation was significantly higher than that of the 21 specimens
negative for p53 gene mutation. Furthermore, the degree of cell
differentiation was significantly correlated with both p53 gene
mutation and high telomerase activity.
p53 gene mutation and high telomerase activity cooperate to induce
tumorigenesis and low-grade differentiation in NSCLC. Simultaneous
occurrence of p53 gene mutation and high telomerase activity may be
relevant to the grade of malignancy in NSCLC.