p53 gene mutations are associated with shortened survival in patients withadvanced non-small cell lung cancer: An analysis of medically managed patients

Mutations in the p53 gene are common in many cancers, Nevertheless, the rel ationship between mutations of this tumor suppressor gene and patient survi val in nonsmall 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 those to examine pat ients 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 mutati ons in cytology or biopsy specimens, to evaluate the prognostic significanc e of p53 gene mutations in nonsurgical patients with advanced PI;SCLC, Zn 7 0 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 t hose without mutations (median survival, 17 versus 39 weeks; P = 0.0003) in dependent of other clinical factors. This abbreviated survival occurred in both patients who received chemotherapy (n = 39, P = 0.002) or best support ive 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 porte nds a significantly worse prognosis.