MSH2/BRCA1 expression as a DNA-repair signature predicting survival in early-stage lung cancer patients from the IFCT-0002 Phase 3 Trial

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TitreMSH2/BRCA1 expression as a DNA-repair signature predicting survival in early-stage lung cancer patients from the IFCT-0002 Phase 3 Trial
Type de publicationJournal Article
Year of Publication2017
AuteursLevallet G, Dubois F, Fouret P, Antoine M, Brosseau S, Bergot E, Beau-Faller M, Gounant V, Brambilla E, Debieuvre D, Molinier O, Galateau-Salle F, Mazieres J, Quoix E, Pujol J-L, Moro-Sibilot D, Langlais A, Morin F, Westeel V, Zalcman G
JournalONCOTARGET
Volume8
Pagination4313-4329
Date PublishedJAN 17
Type of ArticleArticle
Mots-clésBRCA1, MGMT, MSH2, neo-adjuvant chemotherapy, Non-small cell lung cancer
Résumé

{Introduction: DNA repair is a double-edged sword in lung carcinogenesis. When defective, it promotes genetic instability and accumulated genetic alterations. Conversely these defects could sensitize cancer cells to therapeutic agents inducing DNA breaks. Methods: We used immunohistochemistry (IHC) to assess MSH2, XRCC5, and BRCA1 expression in 443 post-chemotherapy specimens from patients randomized in a Phase 3 trial, comparing two neoadjuvant regimens in 528 Stage I-II non-small cell lung cancer (NSCLC) patients (IFCT-0002). O6MGMT promoter gene methylation was analyzed in a subset of 208 patients of the same trial with available snap-frozen specimens. Results: Median follow-up was from 90 months onwards. Only high BRCA1 (n = 221, hazard ratio [HR] = 1.58, 95% confidence interval [CI] [1.07-2.34]
DOI10.18632/oncotarget.14025