Anne-Claire Toffart1, Jean-François Timsit2, Sébastien Couraud3, Patrick Merle4, Denis Moro-Sibilot5, Maurice Perol6, Bénédicte Mastroianni7, Pierre-Jean Souquet3, Nicolas Girard8, Gaëlle Jeannin9, Philippe Romand10, Patrick Chatellain11, Aurélien Vesin12, Christian Brambilla5, Elisabeth Brambilla13. 1. Université Grenoble 1, INSERM, U 823, Institut A Bonniot, Université J Fourier, Rond-point de la Chantourne, 38706 La Tronche Cedex, France; Thoracic Oncology Unit, Teaching Hospital A Michallon, BP217, 38043 Grenoble Cedex 9, France. Electronic address: AToffart@chu-grenoble.fr. 2. Université Grenoble 1, INSERM, U 823, Institut A Bonniot, Université J Fourier, Rond-point de la Chantourne, 38706 La Tronche Cedex, France; Medical Intensive Care Unit, Teaching Hospital A Michallon, BP217, 38043 Grenoble Cedex 9, France. 3. Pulmonology Department, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, 69495 Pierre Bénite Cedex, France; Lyon Sud Faculty of Medicine, Lyon 1 University, 165 chemin du Petit Revoyet, BP 12, 69921 Oullins Cedex, France. 4. Respiratory Medicine, Thoracic Oncology Unit, Centre Hospitalier Universitaire G. Montpied, 58 Rue Montalembert, 63003 Clermont Ferrand Cedex 1, France; EA 7283, Université d'Auvergne, INSERM CIC 501, Bât.3C, Faculté de médecine, 63001 Clermont-Ferrand Cedex, France. 5. Université Grenoble 1, INSERM, U 823, Institut A Bonniot, Université J Fourier, Rond-point de la Chantourne, 38706 La Tronche Cedex, France; Thoracic Oncology Unit, Teaching Hospital A Michallon, BP217, 38043 Grenoble Cedex 9, France. 6. Thoracic Oncology Unit, Croix-Rousse Hospital, Hospices Civils de Lyon, 103 Grande Rue de la Croix-Rousse, 69317 Lyon Cedex 04, France. 7. Respiratory Medicine Service, Hôpital Louis Pradel, Hospices Civils de Lyon, 59 boulevard Pinel, 69677 Bron Cedex, France. 8. Respiratory Medicine Service, Hôpital Louis Pradel, Hospices Civils de Lyon, 59 boulevard Pinel, 69677 Bron Cedex, France; Université Claude Bernard Lyon 1, 43 boulevard du 11 Novembre 1918, 69622 Villeurbanne Cedex, France. 9. Respiratory Medicine, Thoracic Oncology Unit, Centre Hospitalier Universitaire G. Montpied, 58 Rue Montalembert, 63003 Clermont Ferrand Cedex 1, France. 10. Respiratory Medicine Service, Hôpitaux du Leman, 3 avenue de la Dame, BP 526, 74203 Thonon Les Bains, France. 11. Respiratory Medicine Service, Centre Hospitalier Alpes Leman, 558 route de Findrol, BP 20 500, 74130 Contamine sur Arve, France. 12. Université Grenoble 1, INSERM, U 823, Institut A Bonniot, Université J Fourier, Rond-point de la Chantourne, 38706 La Tronche Cedex, France. 13. Université Grenoble 1, INSERM, U 823, Institut A Bonniot, Université J Fourier, Rond-point de la Chantourne, 38706 La Tronche Cedex, France; Department of Pathology, Teaching Hospital A Michallon, BP217, 38043 Grenoble Cedex 9, France.
Abstract
OBJECTIVES: Platinum-based chemotherapy regimens are the standard treatment of non-small cell lung cancer (NSCLC). In this study, our objective was to identify tumor tissue protein biomarkers that might predict a benefit from these treatments. MATERIALS AND METHODS: The Pharmacogenoscan study prospectively included consecutive chemotherapy-naive NSCLC patients at any stage between 2005 and 2010 at six hospitals in the Rhône-Alpes-Auvergne region of France. Of the 537 patients in the full analysis set, 460 had a complete histological diagnosis. We used the tumor tissue samples for an immunohistochemical evaluation of eight biomarkers: ERCC1, BRCA1, p53, p27kip1, class III β-tubulin (TUBB3), Bax, Fas, and FasL. We looked for associations between these biomarkers and the disease control rate (DCR) after 2/3 cycles of platinum-based chemotherapy, progression-free survival (PFS), and overall survival (OS). RESULTS: A tissue sample adequate for testing at least one biomarker was available for 289 patients. We found no significant association between biomarker expression levels and clinical or pathological variables; TUBB3 showed a trend toward higher expression in adenocarcinomas (P=0.005). For none of the biomarkers were significant associations found between expression level and DCR, PFS, or OS. TUBB3-negative and FasL-negative tumors showed associations of borderline significance with higher DCR. CONCLUSION: In a large cohort of patients with predominantly advanced or metastatic NSCLC, none of eight tested immunohistochemical biomarkers predicted the chemotherapy response or survival. Our data indicate limited usefulness of protein biomarkers in metastatic NSCLC and a need for further research based on molecular signatures of greater complexity.
OBJECTIVES:Platinum-based chemotherapy regimens are the standard treatment of non-small cell lung cancer (NSCLC). In this study, our objective was to identify tumor tissue protein biomarkers that might predict a benefit from these treatments. MATERIALS AND METHODS: The Pharmacogenoscan study prospectively included consecutive chemotherapy-naive NSCLCpatients at any stage between 2005 and 2010 at six hospitals in the Rhône-Alpes-Auvergne region of France. Of the 537 patients in the full analysis set, 460 had a complete histological diagnosis. We used the tumor tissue samples for an immunohistochemical evaluation of eight biomarkers: ERCC1, BRCA1, p53, p27kip1, class III β-tubulin (TUBB3), Bax, Fas, and FasL. We looked for associations between these biomarkers and the disease control rate (DCR) after 2/3 cycles of platinum-based chemotherapy, progression-free survival (PFS), and overall survival (OS). RESULTS: A tissue sample adequate for testing at least one biomarker was available for 289 patients. We found no significant association between biomarker expression levels and clinical or pathological variables; TUBB3 showed a trend toward higher expression in adenocarcinomas (P=0.005). For none of the biomarkers were significant associations found between expression level and DCR, PFS, or OS. TUBB3-negative and FasL-negative tumors showed associations of borderline significance with higher DCR. CONCLUSION: In a large cohort of patients with predominantly advanced or metastatic NSCLC, none of eight tested immunohistochemical biomarkers predicted the chemotherapy response or survival. Our data indicate limited usefulness of protein biomarkers in metastatic NSCLC and a need for further research based on molecular signatures of greater complexity.
Authors: Maroulio Pertesi; Perrine Galia; Nicolas Nazaret; Maxime Vallée; Laurent Garderet; Xavier Leleu; Hervé Avet-Loiseau; Matthieu Foll; Graham Byrnes; Joel Lachuer; James D McKay; Charles Dumontet Journal: PLoS One Date: 2015-09-09 Impact factor: 3.240
Authors: F Grossi; E Rijavec; C Genova; G Barletta; F Biello; C Maggioni; G Burrafato; C Sini; M G Dal Bello; K Meyer; J Roder; H Roder; J Grigorieva Journal: Br J Cancer Date: 2016-11-29 Impact factor: 7.640