Nondisruptive p53 mutations are associated with shorter survival in patients with advanced non-small cell lung cancer

Miguel A. Molina-Vila, Jordi Bertran-Alamillo, Amaya Gascó, Clara Mayo-de-las-Casas, María Sánchez-Ronco, Laia Pujantell-Pastor, Laura Bonanno, Adolfo G. Favaretto, Andrés F. Cardona, Alain Vergnenègre, Margarita Majem, Bartomeu Massuti, Teresa Morán, Enric Carcereny, Santiago Viteri, Rafael Rosell

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE: TP53 mutations in early-stage non-small cell lung cancer (NSCLC) may be associated with worse survival but their prognostic role in advanced NSCLC is controversial. In addition, it remains unclear whether mutated patients represent a clinically homogeneous group.

EXPERIMENTAL DESIGN: We retrospectively examined TP53 mutations and outcome in a training cohort of 318 patients with stage IIIB-IV NSCLC: 125 epidermal growth factor receptor (EGFR) wild-type (wt) and 193 EGFR mutated (mut). An independent validation cohort of 64 EGFR-mut patients was subsequently analyzed. Mutations were classified as "disruptive" and "nondisruptive" according to their predicted degree of disturbance of the p53 protein structure and function.

RESULTS: In the training cohort, TP53 mutations were found in 43 of the 125 EGFR-wt patients (34.4%). Of these, 28 had nondisruptive TP53 mutations and a median overall survival (OS) of 8.5 months, compared with 15.6 months for the remaining 97 patients (P=0.003). In the EGFR-mut group, TP53 mutations were found in 50 of the 193 patients (25.9%). The OS for the 26 patients with TP53 nondisruptive mutations was 17.8 months versus 28.4 months for the remaining 167 patients (P=0.04). In the validation cohort, the 11 patients with nondisruptive TP53 mutations had a median OS of 18.1 months compared with 37.8 months for the 53 remaining patients (P=0.006). In multivariate analyses, nondisruptive TP53 mutations had an independent, significant association with a shorter OS.

CONCLUSIONS: Nondisruptive mutations in the TP53 gene are an independent prognostic factor of shorter survival in advanced NSCLC.

Original languageEnglish
Pages (from-to)4647-4659
Number of pages13
JournalClinical Cancer Research
Volume20
Issue number17
DOIs
Publication statusPublished - Sep 1 2014

ASJC Scopus subject areas

  • Medicine(all)

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