Prognostic and predictive importance of p53 and RAS for adjuvant chemotherapy in non-small-cell lung cancer

Ming Sound Tsao, Sarit Aviel-Ronen, Keyue Ding, Davina Lau, Ni Liu, Akira Sakurada, Marlo Whitehead, Chang Qi Zhu, Robert Livingston, David H. Johnson, James Rigas, Lesley Seymour, Timothy Winton, Frances A. Shepherd

研究成果: Article査読

239 被引用数 (Scopus)

抄録

Purpose: p53 and RAS are multifunctional proteins that are critical to cell cycle regulation, apoptosis, cell survival, gene transcription, response to stress, and DNA repair. We have evaluated the prognostic and predictive value of p53 gene/protein aberrations using tumor samples from JBR.10, a North American phase III intergroup trial that randomly assigned 482 patients with completely resected stage IB and II non-small-cell lung cancer (NSCLC) to receive four cycles of adjuvant cisplatin plus vinorelbine or observation alone. Methods: p53 protein expression was evaluated by immunohistochemistry. Mutations in exons 5 to 9 of the p53 gene were determined by denaturing high-performance liquid chromatography and confirmed by sequencing. RAS mutations were identified by allelic specific oligonucleotide hybridization. Results: Of 253 patients, 132 (52%) were positive for p53 protein overexpression. Untreated p53-positive patients had significantly shorter overall survival than did patients with p53-negative tumors (hazard ratio [HR] = 1.89; 95% CI, 1.07 to 3.34; P = .03). However, these p53-positive patients also had a significantly greater survival benefit from adjuvant chemotherapy (HR = 0.54; P = .02) compared with patients with p53-negative tumors (HR = 1.40; P = .26; interaction P = .02). Mutations of p53 and RAS genes were found in 124 (31%) of 397 and 117 (26%) of 450 patients, respectively. Mutations in these genes were neither prognostic for survival nor predictive of a differential benefit from adjuvant chemotherapy. Conclusion: p53 protein overexpression is a significant prognostic marker of shortened survival, and also a significant predictive marker for a differentially greater benefit from adjuvant chemotherapy in completely resected NSCLC patients.

本文言語English
ページ(範囲)5240-5247
ページ数8
ジャーナルJournal of Clinical Oncology
25
33
DOI
出版ステータスPublished - 2007 11 20
外部発表はい

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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