BACKGROUND: The p53 gene is frequently mutated in non-small-cell lung cancer (NSCLC); however, the effect of p53 gene mutations on patient prognosis remains unclear. Therefore, we initiated a prospective study to determine the association of p53 gene mutations with survival in patients with stage I NSCLC. METHODS: Tumor samples were collected prospectively from 188 patients with operable NSCLC (stages I, II, and IIIA). p53 mutations were detected by direct dideoxynucleotide sequencing and p53 GeneChip analysis. Association of clinical and pathologic variables (e.g., alcohol consumption, sex, age, pathologic stage) with mutation of the p53 gene was determined by logistic regression. Associations between p53 mutation status, clinical and pathologic variables, and survival were assessed using a Cox proportional hazards regression model. All statistical tests were two-sided. RESULTS: p53 mutations were detected in 55% (104/188) of tumors. These mutations were associated with non-bronchoalveolar tumors, a history of alcohol consumption, and younger patient age. The risk of death was statistically significantly higher in patients with p53 mutations in their tumors (hazard ratio [HR] = 1.6, 95% confidence interval [CI] = 1.0 to 2.4; P =.049) than in patients with wild-type p53 in their tumors. Tumor stage, the presence of a p53 mutation, and increasing patient age were statistically significant predictors of patient death in the entire patient group; however, the statistically significant prognostic effect of p53 mutation was limited to patients with stage I NSCLC (stage I HR = 2.8, 95% CI = 1.4 to 5.6; stage II HR = 1.8, 95% CI = 0.74 to 4.4; and stage III HR = 0.70, 95% CI = 0.32 to 1.5). Among patients with stage I NSCLC, actuarial 4-year survival was statistically significantly higher in those with wild-type p53 than in those with mutant p53 (78% versus 52%, respectively; difference in 4-year survival = 26%, 95% CI = 6% to 46%; P =.009, log-rank test). CONCLUSION: Tumor p53 mutations are a statistically significant predictor of poor outcome in patients with stage I NSCLC.
BACKGROUND: The p53 gene is frequently mutated in non-small-cell lung cancer (NSCLC); however, the effect of p53 gene mutations on patient prognosis remains unclear. Therefore, we initiated a prospective study to determine the association of p53 gene mutations with survival in patients with stage I NSCLC. METHODS: Tumor samples were collected prospectively from 188 patients with operable NSCLC (stages I, II, and IIIA). p53 mutations were detected by direct dideoxynucleotide sequencing and p53 GeneChip analysis. Association of clinical and pathologic variables (e.g., alcohol consumption, sex, age, pathologic stage) with mutation of the p53 gene was determined by logistic regression. Associations between p53 mutation status, clinical and pathologic variables, and survival were assessed using a Cox proportional hazards regression model. All statistical tests were two-sided. RESULTS:p53 mutations were detected in 55% (104/188) of tumors. These mutations were associated with non-bronchoalveolar tumors, a history of alcohol consumption, and younger patient age. The risk of death was statistically significantly higher in patients with p53 mutations in their tumors (hazard ratio [HR] = 1.6, 95% confidence interval [CI] = 1.0 to 2.4; P =.049) than in patients with wild-type p53 in their tumors. Tumor stage, the presence of a p53 mutation, and increasing patient age were statistically significant predictors of patientdeath in the entire patient group; however, the statistically significant prognostic effect of p53 mutation was limited to patients with stage I NSCLC (stage I HR = 2.8, 95% CI = 1.4 to 5.6; stage II HR = 1.8, 95% CI = 0.74 to 4.4; and stage III HR = 0.70, 95% CI = 0.32 to 1.5). Among patients with stage I NSCLC, actuarial 4-year survival was statistically significantly higher in those with wild-type p53 than in those with mutant p53 (78% versus 52%, respectively; difference in 4-year survival = 26%, 95% CI = 6% to 46%; P =.009, log-rank test). CONCLUSION: Tumor p53 mutations are a statistically significant predictor of poor outcome in patients with stage I NSCLC.
Authors: Zhao Chen; Katherine Cheng; Zandra Walton; Yuchuan Wang; Hiromichi Ebi; Takeshi Shimamura; Yan Liu; Tanya Tupper; Jing Ouyang; Jie Li; Peng Gao; Michele S Woo; Chunxiao Xu; Masahiko Yanagita; Abigail Altabef; Shumei Wang; Charles Lee; Yuji Nakada; Christopher G Peña; Yanping Sun; Yoko Franchetti; Catherine Yao; Amy Saur; Michael D Cameron; Mizuki Nishino; D Neil Hayes; Matthew D Wilkerson; Patrick J Roberts; Carrie B Lee; Nabeel Bardeesy; Mohit Butaney; Lucian R Chirieac; Daniel B Costa; David Jackman; Norman E Sharpless; Diego H Castrillon; George D Demetri; Pasi A Jänne; Pier Paolo Pandolfi; Lewis C Cantley; Andrew L Kung; Jeffrey A Engelman; Kwok-Kin Wong Journal: Nature Date: 2012-03-18 Impact factor: 49.962
Authors: Yanding Zhao; Frederick S Varn; Guoshuai Cai; Feifei Xiao; Christopher I Amos; Chao Cheng Journal: Cancer Epidemiol Biomarkers Prev Date: 2017-11-15 Impact factor: 4.254
Authors: Leelakumari Sreeja; Volga S Syamala; Vani Syamala; Sreedharan Hariharan; Praveenkumar B Raveendran; R V Vijayalekshmi; Jayaprakash Madhavan; Ravindran Ankathil Journal: J Cancer Res Clin Oncol Date: 2007-10-19 Impact factor: 4.553
Authors: Celia A Kanashiro; Andrew V Schally; Kate Groot; Patricia Armatis; Andrea L F Bernardino; Jozsef L Varga Journal: Proc Natl Acad Sci U S A Date: 2003-12-05 Impact factor: 11.205