title: p53 gene mutations are associated with shortened survival in patients with advanced non-small cell lung cancer: an analysis of medically managed patients.
abstract: Mutations in the p53 gene are common in many cancers. Nevertheless, the relationship between mutations of this tumor suppressor gene and patient survival in non-small cell lung cancer (NSCLC) remains unclear. Interpretation of prior studies of patient outcomes are complicated by the inclusion of both surgical and nonsurgical patients. To better isolate the potential effects of p53 gene mutations per se on tumor progression, we chose to examine patients with advanced disease in whom surgery was not performed (stages IIIA, IIIB, and IV). We have used PCR-denaturing gradient gel electrophoresis, a sensitive and specific method for the detection of a variety of p53 mutations in cytology or biopsy specimens, to evaluate the prognostic significance of p53 gene mutations in nonsurgical patients with advanced NSCLC. In 70 consecutive medical patients, p53 mutations were found in 29 cases (41%) at the time of initial diagnosis. Followed prospectively, patients with p53 mutations had a significantly reduced survival time after diagnosis than those without mutations (median survival, 17 versus 39 weeks; P = 0.0003) independent of other clinical factors. This abbreviated survival occurred in both patients who received chemotherapy (n = 39, P = 0.002) or best supportive care (n = 31, P = 0.018). These results indicate that mutations of the p53 gene in patients with NSCLC who do not undergo surgical resection portends a significantly worse prognosis.
authors.affiliation: Department of Internal Medicine, National Hiroshima Hospital, Higashi, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Murakami
authors.forename: K
authors.initials: K
authors.lastname: Hiyama
authors.forename: S
authors.initials: S
authors.lastname: Ishioka
authors.forename: M
authors.initials: M
authors.lastname: Yamakido
authors.forename: F
authors.initials: F
authors.lastname: Kasagi
authors.forename: Y
authors.initials: Y
authors.lastname: Yokosaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005091:Exons; D005260:Female; D016158:Genes, p53; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D012907:Smoking; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents