p53 mutations and survival in stage I non-small-cell lung cancer

Results of a prospective study

Steven A. Ahrendt, Yingchuan Hu, Martin Buta, Michael P. McDermott, Nicole Benoit, Stephen C Yang, Li Wu, David Sidransky

Research output: Contribution to journalArticle

Abstract

Background: The p53 gene is frequently mutated in nonsmall-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 nonbronchoalveolar 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.

Original languageEnglish (US)
Pages (from-to)961-970
Number of pages10
JournalJournal of the National Cancer Institute
Volume95
Issue number13
StatePublished - Jul 2 2003

Fingerprint

Non-Small Cell Lung Carcinoma
Prospective Studies
Mutation
Survival
p53 Genes
Confidence Intervals
Neoplasms
Alcohol Drinking
Dideoxynucleotides
Proportional Hazards Models
Logistic Models

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

p53 mutations and survival in stage I non-small-cell lung cancer : Results of a prospective study. / Ahrendt, Steven A.; Hu, Yingchuan; Buta, Martin; McDermott, Michael P.; Benoit, Nicole; Yang, Stephen C; Wu, Li; Sidransky, David.

In: Journal of the National Cancer Institute, Vol. 95, No. 13, 02.07.2003, p. 961-970.

Research output: Contribution to journalArticle

Ahrendt, Steven A. ; Hu, Yingchuan ; Buta, Martin ; McDermott, Michael P. ; Benoit, Nicole ; Yang, Stephen C ; Wu, Li ; Sidransky, David. / p53 mutations and survival in stage I non-small-cell lung cancer : Results of a prospective study. In: Journal of the National Cancer Institute. 2003 ; Vol. 95, No. 13. pp. 961-970.
@article{a80d210200be4d41aa23c0af0a210c83,
title = "p53 mutations and survival in stage I non-small-cell lung cancer: Results of a prospective study",
abstract = "Background: The p53 gene is frequently mutated in nonsmall-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 nonbronchoalveolar 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.",
author = "Ahrendt, {Steven A.} and Yingchuan Hu and Martin Buta and McDermott, {Michael P.} and Nicole Benoit and Yang, {Stephen C} and Li Wu and David Sidransky",
year = "2003",
month = "7",
day = "2",
language = "English (US)",
volume = "95",
pages = "961--970",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "13",

}

TY - JOUR

T1 - p53 mutations and survival in stage I non-small-cell lung cancer

T2 - Results of a prospective study

AU - Ahrendt, Steven A.

AU - Hu, Yingchuan

AU - Buta, Martin

AU - McDermott, Michael P.

AU - Benoit, Nicole

AU - Yang, Stephen C

AU - Wu, Li

AU - Sidransky, David

PY - 2003/7/2

Y1 - 2003/7/2

N2 - Background: The p53 gene is frequently mutated in nonsmall-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 nonbronchoalveolar 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.

AB - Background: The p53 gene is frequently mutated in nonsmall-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 nonbronchoalveolar 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.

UR - http://www.scopus.com/inward/record.url?scp=0042964835&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0042964835&partnerID=8YFLogxK

M3 - Article

VL - 95

SP - 961

EP - 970

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 13

ER -