© 2003 by Oxford University Press
Journal of the National Cancer Institute, Vol. 95, No. 13, 961-970,
July 2, 2003
© 2003 Oxford University Press
ARTICLE |
p53 Mutations and Survival in Stage I Non-Small-Cell Lung Cancer: Results of a Prospective Study
Affiliations of authors: S. A. Ahrendt, Y. Hu, Department of Surgery, University of Rochester, Rochester, NY; M. Buta, N. Benoit, L. Wu, D. Sidransky, Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins School of Medicine, Baltimore, MD; M. P. McDermott, Department of Biostatistics, University of Rochester; S. C. Yang, Department of Surgery, The Johns Hopkins School of Medicine.
Correspondence to: Steven A. Ahrendt, M.D., Department of Surgery, University of Rochester, 601 Elmwood Ave., Rochester, NY 14642 (e-mail: steven_ahrendt{at}urmc.rochester.edu).
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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. George, R. H. Datar, L. Wu, J. Cai, N. Patten, S. J. Beil, S. Groshen, J. Stein, D. Skinner, P. A. Jones, et al. p53 Gene and Protein Status: The Role of p53 Alterations in Predicting Outcome in Patients With Bladder Cancer J. Clin. Oncol., December 1, 2007; 25(34): 5352 - 5358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Peltonen, J A Welsh, and K H Vahakangas Is there a role for PCR-SSCP among the methods for missense mutation detection of TP53 gene? Human and Experimental Toxicology, January 1, 2007; 26(1): 9 - 18. [Abstract] [PDF]
|
|
|
|
|
|
S. M. Park, M. K. Lim, S. A. Shin, and Y. H. Yun Impact of Prediagnosis Smoking, Alcohol, Obesity, and Insulin Resistance on Survival in Male Cancer Patients: National Health Insurance Corporation Study J. Clin. Oncol., November 1, 2006; 24(31): 5017 - 5024. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Boersma, T. M. Howe, J. E. Goodman, H. G. Yfantis, D. H. Lee, S. J. Chanock, and S. Ambs Association of Breast Cancer Outcome With Status of p53 and MDM2 SNP309. J Natl Cancer Inst, July 5, 2006; 98(13): 911 - 919. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Raz, B. He, R. Rosell, and D. M. Jablons Current concepts in bronchioloalveolar carcinoma biology. Clin. Cancer Res., June 15, 2006; 12(12): 3698 - 3704. [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. Jackson, K. P. Olive, D. A. Tuveson, R. Bronson, D. Crowley, M. Brown, and T. Jacks The Differential Effects of Mutant p53 Alleles on Advanced Murine Lung Cancer Cancer Res., November 15, 2005; 65(22): 10280 - 10288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. H. Nelson, M. Wilkojmen, C. J. Marsit, and K. T. Kelsey TP53 mutation, allelism and survival in non-small cell lung cancer Carcinogenesis, October 1, 2005; 26(10): 1770 - 1773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Paull, G. M. Updyke, M. A. Baumann, H. W. Chin, A. G. Little, and S. A. Adebonojo Alcohol Abuse Predicts Progression of Disease and Death in Patients with Lung Cancer Ann. Thorac. Surg., September 1, 2005; 80(3): 1033 - 1039. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Goggins Molecular Markers of Early Pancreatic Cancer J. Clin. Oncol., July 10, 2005; 23(20): 4524 - 4531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Singhal, A. Vachani, D. Antin-Ozerkis, L. R. Kaiser, and S. M. Albelda Prognostic Implications of Cell Cycle, Apoptosis, and Angiogenesis Biomarkers in Non-Small Cell Lung Cancer: A Review Clin. Cancer Res., June 1, 2005; 11(11): 3974 - 3986. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Marrogi, L. E. Mechanic, J. A. Welsh, E. D. Bowman, M. A. Khan, L. Enewold, P. G. Shields, and C. C. Harris TP53 Mutation Spectrum in Lung Cancer Is Not Different in Women and Men Cancer Epidemiol. Biomarkers Prev., April 1, 2005; 14(4): 1031 - 1033. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hu, M. P. McDermott, and S. A. Ahrendt The p53 Codon 72 Proline Allele Is Associated with p53 Gene Mutations in Non-Small Cell Lung Cancer Clin. Cancer Res., April 1, 2005; 11(7): 2502 - 2509. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Nonaka, A. Fabbri, L. Roz, L. Mariani, A. Vecchione, G. W. Moore, L. Tavecchio, C. M. Croce, and G. Sozzi Reduced FEZ1/LZTS1 Expression and Outcome Prediction in Lung Cancer Cancer Res., February 15, 2005; 65(4): 1207 - 1212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Lu, J.-C. Soria, X. Tang, X.-C. Xu, L. Wang, L. Mao, R. Lotan, B. Kemp, B. N. Bekele, L. Feng, et al. Prognostic Factors in Resected Stage I Non-Small-Cell Lung Cancer: A Multivariate Analysis of Six Molecular Markers J. Clin. Oncol., November 15, 2004; 22(22): 4575 - 4583. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Pellise, A. Castells, A. Gines, R. Agrelo, M. Sole, S. Castellvi-Bel, G. Fernandez-Esparrach, J. Llach, M. Esteller, J. M. Bordas, et al. Detection of Lymph Node Micrometastases by Gene Promoter Hypermethylation in Samples Obtained by Endosonography- Guided Fine-Needle Aspiration Biopsy Clin. Cancer Res., July 1, 2004; 10(13): 4444 - 4449. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-G. Zhu, T. Hileman, Y. Ke, P. Wang, S. Lu, W. Duan, Z. Dai, T. Tong, M. A. Villalona-Calero, C. Plass, et al. 5-Aza-2'-deoxycytidine Activates the p53/p21Waf1/Cip1 Pathway to Inhibit Cell Proliferation J. Biol. Chem., April 9, 2004; 279(15): 15161 - 15166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Kanashiro, A. V. Schally, K. Groot, P. Armatis, A. L. F. Bernardino, and J. L. Varga Inhibition of mutant p53 expression and growth of DMS-153 small cell lung carcinoma by antagonists of growth hormone-releasing hormone and bombesin PNAS, December 23, 2003; 100(26): 15836 - 15841. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Kaye and T. Komiya New Leads Suggest a Clinically Relevant Genotype-Phenotype Relationship for the p53 Gene J Natl Cancer Inst, July 2, 2003; 95(13): 926 - 927. [Full Text] [PDF]
|
|