| Added by | mollevi |
|---|---|
| Last modified by | amaraver |
| Group name | EquipeAM |
| Item Type | Journal Article |
| Title | MSH2/BRCA1 expression as a DNA-repair signature predicting survival in early-stage lung cancer patients from the IFCT-0002 Phase 3 Trial |
| Creator | Levallet et al. |
| Author | G. Levallet |
| Author | F. Dubois |
| Author | P. Fouret |
| Author | M. Antoine |
| Author | S. Brosseau |
| Author | E. Bergot |
| Author | M. Beau-Faller |
| Author | V. Gounant |
| Author | E. Brambilla |
| Author | D. Debieuvre |
| Author | O. Molinier |
| Author | F. Galateau-Salle |
| Author | J. Mazieres |
| Author | E. Quoix |
| Author | J. L. Pujol |
| Author | D. Moro-Sibilot |
| Author | A. Langlais |
| Author | F. Morin |
| Author | V. Westeel |
| Author | G. Zalcman |
| Abstract | 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], p = 0.02) and low MSH2 expression (n = 356, HR = 1.52, 95% CI [1.11-2.08], p = 0.008) significantly predicted better overall survival (OS) in univariate and multivariate analysis. A bootstrap re-sampling strategy distinguished three patient groups at high (n = 55, low BRCA1 and high MSH2, median OS >96 months, HR = 2.5, 95% CI [1.45-4.33], p = 0.001), intermediate (n = 82, median OS = 73.4 p = 0.0596), and low (high BRCA1 and low MSH2, n = 67, median OS = ND, HR = 0.51, 95% CI [0.31-0.83], p = 0.006) risk of death. INTERPRETATION: DNA repair protein expression assessment identified three different groups of risk of death in early-stage lung cancer patients, according to their tumor MSH2 and BRCA1 expression levels. These results deserve prospective evaluation of MSH2/BRCA1 theranostic value in lung cancer patients treated with combinations of DNA-damaging chemotherapy and drugs targeting DNA repair, such as Poly(ADP-ribose) polymerase (PARP) inhibitors. |
| Publication | Oncotarget |
| Date | Dec 19 2016 |
| Journal Abbr | Oncotarget |
| DOI | 10.18632/oncotarget.14025 |
| ISSN | 1949-2553 (Electronic) 1949-2553 (Linking) |
| Tags | clinic |
| Date Added | 2018/11/14 - 12:43:03 |
| Date Modified | 2019/05/16 - 11:02:36 |
| Notes and Attachments | (Note) (Note) 28008145 (Attachment) |
Institut de Recherche en Cancérologie de
