PROGNOSTIC-SIGNIFICANCE OF P53 AND RAS GENE ABNORMALITIES IN LUNG ADENOCARCINOMA PATIENTS WITH STAGE-I DISEASE AFTER CURATIVE RESECTION

We investigated the prognostic significance of p53 gene abnormalities and ras gene mutations in patients with curatively resected stage I lung adenocarcinoma. Formalin-fixed and paraffin-embedded tissues were obtained from 30 patients who had undergone curative resection for stage I lung adenocarcinoma. Abnormalities of the p53 gene were detected using polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analysis and immunohistochemistry and ras mutations were detected using PCR-restriction fragment length polymorphism (RFLP) analysis. Both univariate and multivariate analyses were performed to assess the relationship between the presence of abnormalities of these genes and the patients' disease-free survival. Eleven tumors (37%) had mutated p53 sequences and 11 (37%) showed p53 overexpression. A total of 15 tumors (50%) had p53 gene abnormalities and the concordance rate was 73%. Seven tumors (23%) showed mutated ras sequences. The univariate analysis revealed that the disease-free survival of patients with any p53 abnormality was shorter than that of those without abnormalities (P=0.02, generalized Wilcoxon test), and survival of those with p53 protein overexpression was more significantly shorter (P=0.003, generalized Wilcoxon test). Multivariate analysis using the Cox proportional hazards model indicated that the presence of p53 abnormalities was a significantly (P=0.01) unfavourable prognostic factor. There was no significant correlation between the presence of ras mutation and survival. These results suggest that analysis of the p53 gene may be helpful for the selection of high-risk patients for clinical trials of adjuvant therapy for stage I lung adenocarcinoma.