:. Tumeur, -83 - III. Place de l'immunohistochimie (IHC) dans la détection des mutations du gène de l'EGFR, p.85

I. Biologie-moléculaire-versus-immunohistochimie and :. , -98 - IV. Problématique de l'évaluation de la richesse tumorale, p.100

L. Majorité, 9%) des prélèvements ont été fixés dans du formol à 10% (v/v) tamponné pH 7,4 (n=77), seuls 3 prélèvements ont été fixés dans de l'AFA, Alcool Formolé Acétique), vol.933, p.7

B. 1. Moro-sibilot and D. , Tumeurs du poumon, primitives et secondaires, 2010.

I. Inserm, Dynamique d'évolution des taux de mortalité dans les principaux cancers en France Plan Cancer, 2010.

E. Brambilla, R??ponses aux th??rapies cibl??es??: le cancer du poumon, Annales de Pathologie, vol.29, issue.5, pp.77-80, 2009.
DOI : 10.1016/j.annpat.2009.07.033

D. Flieder, Common Non-Small-Cell Carcinomas and Their Variants, 2008.
DOI : 10.1007/978-0-387-72114-9_4

. Inca, ©Recommandations professionnelles Cancer du poumon non à petites cellules, 2010.

. Abadjian, Histopathologie des organes, 2006.

K. Cotran, C. Travis, and W. D. , Anatomie pathologique, bases morphologiques et physiopathologiques des maladies. 2000: Piccin. 10 International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma, J Thorac Oncol, vol.6, issue.2, pp.244-85, 2011.

W. D. Travis, International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma, Journal of Thoracic Oncology, vol.6, issue.2, pp.244-85, 2004.
DOI : 10.1097/JTO.0b013e318206a221

URL : https://hal.archives-ouvertes.fr/inserm-00561753

O. Lababede, M. Meziane, and T. Rice, Seventh Edition of the Cancer Staging Manual and Stage Grouping of Lung Cancer, Chest, vol.139, issue.1, pp.183-192, 2011.
DOI : 10.1378/chest.10-1099

. R. Oncolor, F. Nowak, J. C. Soria, F. Calvo, and T. , 17. INCa, ©Mutations de l'EGFR dans le cancer du poumon : mise en évidence d'une cible moléculaire permettant un accès spécifique aux thérapies ciblées, Boulogne-Billancourt, Editor Tumour molecular profiling for deciding therapythe French initiative [Clinical and molecular predictors of response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer], Nat Rev Clin Oncol Ann Pathol, vol.18, issue.985, pp.479-86, 2007.

J. L. Reiter, Comparative Genomic Sequence Analysis and Isolation of Human and Mouse Alternative EGFR Transcripts Encoding Truncated Receptor Isoforms, Genomics, vol.71, issue.1, pp.1-20, 2001.
DOI : 10.1006/geno.2000.6341

J. J. Carlson, Epidermal growth factor receptor genomic variation in NSCLC patients receiving tyrosine kinase inhibitor therapy: a systematic review and meta-analysis, Journal of Cancer Research and Clinical Oncology, vol.2, issue.2, pp.135-1483, 2009.
DOI : 10.4161/cc.4.10.2105

T. Mitsudomi and Y. Yatabe, Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer, FEBS Journal, vol.22, issue.2, pp.301-309
DOI : 10.1038/modpathol.2009.2

R. N. Jorissen, Epidermal growth factor receptor: mechanisms of activation and signalling, Experimental Cell Research, vol.284, issue.1, pp.31-53, 2003.
DOI : 10.1016/S0014-4827(02)00098-8

M. Ono and M. Kuwano, Molecular Mechanisms of Epidermal Growth Factor Receptor (EGFR) Activation and Response to Gefitinib and Other EGFR-Targeting Drugs, Clinical Cancer Research, vol.12, issue.24, pp.12-7242, 2006.
DOI : 10.1158/1078-0432.CCR-06-0646

X. Zhang, An Allosteric Mechanism for Activation of the Kinase Domain of Epidermal Growth Factor Receptor, Cell, vol.125, issue.6, pp.1137-1186, 2006.
DOI : 10.1016/j.cell.2006.05.013

K. Suda, K. Tomizawa, and T. Mitsudomi, Biological and clinical significance of KRAS mutations in lung cancer: an oncogenic driver that contrasts with EGFR mutation, Cancer and Metastasis Reviews, vol.15, issue.238, pp.49-60, 2010.
DOI : 10.1097/JTO.0b013e3181914111

A. M. Ruppert, Un regard simple sur la biologie du cancer bronchique??: EGFR, Revue des Maladies Respiratoires, vol.28, issue.4, pp.565-77, 2011.
DOI : 10.1016/j.rmr.2011.03.005

G. Bronte, Driver mutations and differential sensitivity to targeted therapies: a new approach to the treatment of lung adenocarcinoma, Cancer Treatment Reviews, vol.36, issue.3, pp.21-30, 2010.
DOI : 10.1016/S0305-7372(10)70016-5

M. A. Lemmon and J. Schlessinger, Cell Signaling by Receptor Tyrosine Kinases, Cell, vol.141, issue.7, pp.1117-1151, 2010.
DOI : 10.1016/j.cell.2010.06.011

L. Lacroix, [KRAS status versus EGFR status in lung cancer therapy], Bull Cancer, issue.96, pp.75-83, 2009.

Y. Sekido, K. M. Fong, and J. D. Minna, Progress in understanding the molecular pathogenesis of human lung cancer, Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, vol.1378, issue.1, pp.1378-1399, 1998.
DOI : 10.1016/S0304-419X(98)00010-9

B. Brandt, Mechanisms of egfr gene transcription modulation: relationship to cancer risk and therapy response Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib, Clin Cancer Res N Engl J Med, vol.33, issue.2421, pp.12-7252, 2004.

I. Okamoto, P-134 Expression of constitutively activated EGFRvIII in non-small cell lung cancer, Lung Cancer, vol.41, issue.1, pp.50-56, 2003.
DOI : 10.1016/S0169-5002(03)92103-9

W. Pao, EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib, Proceedings of the National Academy of Sciences, vol.293, issue.5531, pp.13306-13317, 2004.
DOI : 10.1126/science.1062538

H. Ji, The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies, Cancer Cell, vol.9, issue.6, pp.485-95, 2006.
DOI : 10.1016/j.ccr.2006.04.022

K. Ohashi, driven by the SP-C promoter, Cancer Science, vol.67, issue.12, pp.1747-53, 2008.
DOI : 10.1111/j.1349-7006.2008.00875.x

T. S. Mok, Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma Somatic EGFR mutation and gene copy gain as predictive biomarkers for response to tyrosine kinase inhibitors in non-small cell lung cancer, N Engl J Med Clin Cancer Res, vol.39, issue.161, pp.361-947, 2009.

Z. Liang, Relationship between EGFR expression, copy number and mutation in lung adenocarcinomas 10: p. 376. 41 Survival impact of epidermal growth factor receptor overexpression in patients with non-small cell lung cancer: a meta-analysis, BMC Cancer Thorax, issue.2, pp.61-140, 2006.

T. Akimoto, Inverse relationship between epidermal growth factor receptor expression and radiocurability of murine carcinomas, Clin Cancer Res, issue.510, pp.2884-90, 1999.

Z. Chen, Correlation of cisplatin sensitivity with differential alteration of EGFR expression in head and neck cancer cells, Anticancer Res, vol.20, issue.2A, pp.899-902, 2000.

A. R. Li, EGFR Mutations in Lung Adenocarcinomas, The Journal of Molecular Diagnostics, vol.10, issue.3, pp.242-250, 2008.
DOI : 10.2353/jmoldx.2008.070178

F. R. Hirsch, Increased Epidermal Growth Factor Receptor Gene Copy Number Detected by Fluorescence In Situ Hybridization Associates With Increased Sensitivity to Gefitinib in Patients With Bronchioloalveolar Carcinoma Subtypes: A Southwest Oncology Group Study, Journal of Clinical Oncology, vol.23, issue.28, pp.23-6838, 2005.
DOI : 10.1200/JCO.2005.01.2823

M. Tiseo, Predictors of gefitinib outcomes in advanced non-small cell lung cancer (NSCLC): study of a comprehensive panel of molecular markers Lung Cancer Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small-cell lung cancer, J Clin Oncol, vol.67, issue.4731, pp.355-60, 2006.

M. S. Tsao, Erlotinib in Lung Cancer ??? Molecular and Clinical Predictors of Outcome, New England Journal of Medicine, vol.353, issue.2, pp.133-177, 2005.
DOI : 10.1056/NEJMoa050736

F. Pinter, Epidermal Growth Factor Receptor (EGFR) High Gene Copy Number and Activating Mutations in Lung Adenocarcinomas Are Not Consistently Accompanied by Positivity for EGFR Protein by Standard Immunohistochemistry, The Journal of Molecular Diagnostics, vol.10, issue.2, pp.160-168, 2008.
DOI : 10.2353/jmoldx.2008.070125

R. Pirker, EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study, The Lancet Oncology, vol.13, issue.1, pp.33-42, 2011.
DOI : 10.1016/S1470-2045(11)70318-7

L. Cheng, Molecular pathology of lung cancer: key to personalized medicine, Modern Pathology, vol.17, issue.3, pp.347-69, 2012.
DOI : 10.1158/1078-0432.CCR-10-2277

T. Mitsudomi and Y. Yatabe, Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer, FEBS Journal, vol.22, issue.2, pp.301-309, 2009.
DOI : 10.1038/modpathol.2009.2

A. F. Gazdar, Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors, Oncogene, vol.19, issue.S1, pp.24-31, 2009.
DOI : 10.1016/j.cell.2006.05.013

K. Politi and T. J. Lynch, Two Sides of the Same Coin: EGFR Exon 19 Deletions and Insertions in Lung Cancer, Clinical Cancer Research, vol.18, issue.6, pp.1490-1492, 2012.
DOI : 10.1158/1078-0432.CCR-11-3282

Y. Yatabe, EGFR mutations and the terminal respiratory unit, Cancer and Metastasis Reviews, vol.109, issue.Suppl 1, pp.23-36, 2010.
DOI : 10.1016/S0002-9440(10)63553-5

H. Shigematsu and A. F. Gazdar, Somatic mutations of epidermal growth factor receptor signaling pathway in lung cancers, International Journal of Cancer, vol.4, issue.2, pp.257-62, 2006.
DOI : 10.1007/978-3-642-60049-4

N. T. Tanner, The role of molecular analyses in the era of personalized therapy for advanced NSCLC, Lung Cancer, vol.76, issue.2, pp.131-138, 2011.
DOI : 10.1016/j.lungcan.2011.11.013

P. S. Hammerman, Kinase Gene Identify a Novel Therapeutic Target in Squamous Cell Lung Cancer, Cancer Discovery, vol.1, issue.1, pp.78-89, 2012.
DOI : 10.1158/2159-8274.CD-11-0005

H. Ji, Epidermal growth factor receptor variant III mutations in lung tumorigenesis and sensitivity to tyrosine kinase inhibitors, Proceedings of the National Academy of Sciences, vol.2, issue.3, pp.7817-7839, 2006.
DOI : 10.1093/neuonc/2.3.159

S. Simonetti, Detection of EGFR mutations with mutation-specific antibodies in stage IV non-small-cell lung cancer Assessment of EGFR mutation status in lung adenocarcinoma by immunohistochemistry using antibodies specific to the two major forms of mutant EGFR, J Transl Med J Mol Diagn, vol.8, issue.2, pp.12-169, 2010.

S. J. An, Identification of enriched driver gene alterations in subgroups of nonsmall cell lung cancer patients based on histology and smoking status Oncogenic transformation by inhibitor-sensitive and -resistant EGFR mutants, PLoS One PLoS Med, vol.7, issue.6 211, p.313, 2005.

A. Kumar, Structure and Clinical Relevance of the Epidermal Growth Factor Receptor in Human Cancer, Journal of Clinical Oncology, vol.26, issue.10, pp.26-1742, 2008.
DOI : 10.1200/JCO.2007.12.1178

A. F. Gazdar, Mutations and addiction to EGFR: the Achilles 'heal' of lung cancers? Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study Erlotinib in previously treated non-small-cell lung cancer Epidermal growth factor receptor mutations and gene amplification in non-small-cell lung cancer: molecular analysis of the IDEAL/INTACT gefitinib trials, Trends Mol Med Lancet Oncol N Engl J Med J Clin Oncol, vol.11, issue.353231, pp.481-487, 2004.

W. Pao and J. Chmielecki, Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer, Nature Reviews Cancer, vol.30, issue.11, pp.760-74, 2010.
DOI : 10.1371/journal.pmed.0040315

R. Rosell, Screening for Epidermal Growth Factor Receptor Mutations in Lung Cancer, New England Journal of Medicine, vol.361, issue.10, pp.361-958, 2009.
DOI : 10.1056/NEJMoa0904554

V. D. Cataldo, Treatment of Non???Small-Cell Lung Cancer with Erlotinib or Gefitinib, New England Journal of Medicine, vol.364, issue.10, pp.364-947, 2011.
DOI : 10.1056/NEJMct0807960

D. M. Jackman, Exon 19 Deletion Mutations of Epidermal Growth Factor Receptor Are Associated with Prolonged Survival in Non-Small Cell Lung Cancer Patients Treated with Gefitinib or Erlotinib, Clinical Cancer Research, vol.12, issue.13, pp.12-3908, 2006.
DOI : 10.1158/1078-0432.CCR-06-0462

S. Kobayashi, EGFR mutation and resistance of non-small-cell lung cancer to gefitinib, N Engl J Med, issue.8, pp.352-786, 2005.

C. H. Yun, The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP, Proceedings of the National Academy of Sciences, vol.60, issue.Pt 8, pp.2070-2075, 2008.
DOI : 10.1107/S0907444904011679

W. Pao, Acquired Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib Is Associated with a Second Mutation in the EGFR Kinase Domain, PLoS Medicine, vol.9, issue.3, pp.316-1039, 2005.
DOI : 10.1371/journal.pmed.0020073.sd001

Y. J. Lee, Lung cancer in never smokers: Change of a mindset in the molecular era, Lung Cancer, vol.72, issue.1, pp.9-15, 2011.
DOI : 10.1016/j.lungcan.2010.12.013

M. N. Balak, Novel D761Y and Common Secondary T790M Mutations in Epidermal Growth Factor Receptor-Mutant Lung Adenocarcinomas with Acquired Resistance to Kinase Inhibitors, Clinical Cancer Research, vol.12, issue.21, pp.6494-501, 2006.
DOI : 10.1158/1078-0432.CCR-06-1570

D. B. Costa, To re-treat or not with gefitinib/erlotinib: This is the question for tyrosine kinase inhibitor-responsive lung cancers that progress, Lung Cancer, vol.57, issue.2, pp.251-253, 2007.
DOI : 10.1016/j.lungcan.2007.04.013

H. Yokouchi, Clinical benefit of readministration of gefitinib for initial gefitinib-responders with non-small cell lung cancer, BMC Cancer, vol.16, issue.1, p.95, 2007.
DOI : 10.1093/annonc/mdi369

Y. Kozu, The usefulness of mutation-specific antibodies in detecting epidermal growth factor receptor mutations and in predicting response to tyrosine kinase inhibitor therapy in lung adenocarcinoma, Lung Cancer, vol.73, issue.1, pp.45-50, 2010.
DOI : 10.1016/j.lungcan.2010.11.003

K. S. Funabashi, DNA extraction and molecular analysis of non-tumoral liver, spleen, and brain from autopsy samples: The effect of formalin fixation and paraffin embedding, Pathology - Research and Practice, vol.208, issue.10, 2012.
DOI : 10.1016/j.prp.2012.07.001

C. E. Greer, PCR amplification from paraffin-embedded tissues. Effects of fixative and fixation time, Am J Clin Pathol, issue.2, pp.95-117, 1991.
DOI : 10.1097/00019606-199409000-00015

J. Zhao, A novel method for detection of mutation in epidermal growth factor receptor, Lung Cancer, vol.74, issue.2, pp.226-258, 2011.
DOI : 10.1016/j.lungcan.2011.02.015

J. Yu, Mutation-Specific Antibodies for the Detection of EGFR Mutations in Non-Small-Cell Lung Cancer, Clinical Cancer Research, vol.15, issue.9, pp.3023-3031, 2009.
DOI : 10.1158/1078-0432.CCR-08-2739

M. I. Ilie, Usefulness of tissue microarrays for assessment of protein expression, gene copy number and mutational status of EGFR in lung adenocarcinoma Molecular diagnosis of activating EGFR mutations in non-small cell lung cancer using mutation-specific antibodies for immunohistochemical analysis Immunohistochemical detection of EGFR mutation using mutation-specific antibodies in lung cancer, Virchows Arch Clin Cancer Res Clin Cancer Res, vol.457, issue.161213, pp.483-95, 2010.

C. J. Der, T. G. Krontiris, and G. M. Cooper, Transforming genes of human bladder and lung carcinoma cell lines are homologous to the ras genes of Harvey and Kirsten sarcoma viruses., Proceedings of the National Academy of Sciences, vol.79, issue.11, pp.79-3637, 1982.
DOI : 10.1073/pnas.79.11.3637

J. E. Declue, Abnormal regulation of mammalian p21ras contributes to malignant tumor growth in von Recklinghausen (type 1) neurofibromatosis The ras gene family and human carcinogenesis, Cell Bos, J.L. Mutat Res, vol.69, issue.953, pp.265-73, 1988.

M. Trahey and F. Mccormick, A cytoplasmic protein stimulates normal N-ras p21

M. D. Gtpase, Polyisoprenylation of Ras in vitro by a farnesyl-protein transferase, Science J Biol Chem, issue.482625, pp.238-542, 1987.

J. Avruch, Ras Activation of the Raf Kinase: Tyrosine Kinase Recruitment of the MAP Kinase Cascade, Recent Progress in Hormone Research, vol.56, issue.1, pp.127-55, 2001.
DOI : 10.1210/rp.56.1.127

E. Santos, Malignant activation of a K-ras oncogene in lung carcinoma but not in normal tissue of the same patient, Science, vol.223, issue.4637, pp.223-661, 1984.
DOI : 10.1126/science.6695174

S. Rodenhuis, Mutational activation of the K-ras oncogene and the effect of chemotherapy in advanced adenocarcinoma of the lung: a prospective study., Journal of Clinical Oncology, vol.15, issue.1, pp.285-91, 1997.
DOI : 10.1200/JCO.1997.15.1.285

A. Marchetti, BRONCHIOLOALVEOLAR LUNG CARCINOMAS: K-ras MUTATIONS ARE CONSTANT EVENTS IN THE MUCINOUS SUBTYPE, The Journal of Pathology, vol.17, issue.3, pp.254-263, 1996.
DOI : 10.1097/00000478-199307000-00010

T. Kosaka, Gene in Lung Cancer, Cancer Research, vol.64, issue.24, pp.8919-8942, 2004.
DOI : 10.1158/0008-5472.CAN-04-2818

H. Shigematsu, Clinical and Biological Features Associated With Epidermal Growth Factor Receptor Gene Mutations in Lung Cancers, JNCI Journal of the National Cancer Institute, vol.21, issue.3, pp.339-385, 2005.
DOI : 10.1002/humu.10177

T. Kosaka, Prognostic Implication of EGFR, KRAS, and TP53 Gene Mutations in a Large Cohort of Japanese Patients with Surgically Treated Lung Adenocarcinoma, Journal of Thoracic Oncology, vol.4, issue.1, pp.22-31, 2009.
DOI : 10.1097/JTO.0b013e3181914111

C. Mascaux, The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis, British Journal of Cancer, vol.27, issue.Suppl 3, pp.131-140, 2005.
DOI : 10.1016/S0033-0620(85)80003-7

Y. Loriot, Are RAS mutations predictive markers of resistance to standard chemotherapy?, Nature Reviews Clinical Oncology, vol.96, issue.9, pp.528-562, 2009.
DOI : 10.1080/13651820802029427

D. A. Eberhard, Mutations in the Epidermal Growth Factor Receptor and in KRAS Are Predictive and Prognostic Indicators in Patients With Non???Small-Cell Lung Cancer Treated With Chemotherapy Alone and in Combination With Erlotinib, Journal of Clinical Oncology, vol.23, issue.25, pp.23-5900, 2005.
DOI : 10.1200/JCO.2005.02.857

C. Mao, KRAS mutations and resistance to EGFR-TKIs treatment in patients with non-small cell lung cancer: A meta-analysis of 22 studies, Lung Cancer, vol.69, issue.3, pp.272-280, 2009.
DOI : 10.1016/j.lungcan.2009.11.020

H. Linardou, Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer, The Lancet Oncology, vol.9, issue.10, pp.962-72, 2008.
DOI : 10.1016/S1470-2045(08)70206-7

M. Filipits and R. Pirker, Predictive markers in the adjuvant therapy of non-small cell lung cancer, Lung Cancer, vol.74, issue.3, pp.355-63, 2011.
DOI : 10.1016/j.lungcan.2011.06.005

W. Pao and N. Girard, New driver mutations in non-small-cell lung cancer, The Lancet Oncology, vol.12, issue.2, pp.175-80, 2011.
DOI : 10.1016/S1470-2045(10)70087-5

P. Heinmoller, HER2 status in non-small cell lung cancer (NSCLC): results from the patient screening for enrolment to a phase 2 study of herceptin, European Journal of Cancer, vol.37, issue.914, pp.5238-5281, 2003.
DOI : 10.1016/S0959-8049(01)80666-3

H. Shigematsu, Kinase Domain in Lung Adenocarcinomas, Cancer Research, vol.65, issue.5, pp.1642-1648, 2005.
DOI : 10.1158/0008-5472.CAN-04-4235

K. Tomizawa, Prognostic and predictive implications of HER2/ERBB2/neu gene mutations in lung cancers, Lung Cancer, vol.74, issue.1, pp.139-183, 2011.
DOI : 10.1016/j.lungcan.2011.01.014

S. W. Han, Optimization of Patient Selection for Gefitinib in Non-Small Cell Lung Cancer by Combined Analysis of Epidermal Growth Factor Receptor Mutation, K-ras Mutation, and Akt Phosphorylation, Clinical Cancer Research, vol.12, issue.8, pp.12-2538, 2006.
DOI : 10.1158/1078-0432.CCR-05-2845

S. E. Wang, HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors, Cancer Cell, vol.10, issue.1, pp.25-38, 2006.
DOI : 10.1016/j.ccr.2006.05.023

F. Cappuzzo, L. Bemis, and M. Varella-garcia, HER2 mutation and response to trastuzumab therapy in non-small-cell lung cancer, N Engl J Med, issue.24, pp.354-2619, 2006.

D. Planchard and E. Giroux-leprieur, Biomarqueurs et th??rapies cibl??es dans le cancer bronchique non ?? petites cellules : traitement d???aujourd???hui et de demain, Revue de Pneumologie Clinique, vol.67, issue.1, pp.36-40, 2011.
DOI : 10.1016/S0761-8417(11)70009-8

S. A. Yousem, M. Nikiforova, and Y. Nikiforov, The Histopathology of BRAF-V600E???mutated Lung Adenocarcinoma, The American Journal of Surgical Pathology, vol.32, issue.9, pp.1317-1338, 2008.
DOI : 10.1097/PAS.0b013e31816597ca

G. Scagliotti, Phase III Study of Carboplatin and Paclitaxel Alone or With Sorafenib in Advanced Non???Small-Cell Lung Cancer, Journal of Clinical Oncology, vol.28, issue.11, pp.28-1835, 2010.
DOI : 10.1200/JCO.2009.26.1321

S. Kang, A. G. Bader, and P. K. Vogt, Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic, Proceedings of the National Academy of Sciences, vol.31, issue.3 Suppl 9, pp.802-809, 2005.
DOI : 10.1073/pnas.0405220101

H. Yamamoto, PIK3CA Mutations and Copy Number Gains in Human Lung Cancers, Cancer Research, vol.68, issue.17, pp.6913-6934, 2008.
DOI : 10.1158/0008-5472.CAN-07-5084

V. Ludovini, Phosphoinositide-3-Kinase Catalytic Alpha and KRAS Mutations are Important Predictors of Resistance to Therapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients with Advanced Non-small Cell Lung Cancer, Journal of Thoracic Oncology, vol.6, issue.4, pp.707-722, 2011.
DOI : 10.1097/JTO.0b013e31820a3a6b

K. D. Courtney, R. B. Corcoran, and J. A. Engelman, The PI3K Pathway As Drug Target in Human Cancer, Journal of Clinical Oncology, vol.28, issue.6, pp.28-1075, 2010.
DOI : 10.1200/JCO.2009.25.3641

J. A. Engelman, Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers, Nature Medicine, vol.13, issue.12, pp.14-1351, 2008.
DOI : 10.1128/MCB.18.3.1379

M. Soda, Identification of the transforming EML4-ALK fusion gene in nonsmall-cell lung cancer, Nature, issue.7153, pp.448-561, 2007.

R. Jokoji, Combination of morphological feature analysis and immunohistochemistry is useful for screening of EML4-ALK-positive lung adenocarcinoma, Journal of Clinical Pathology, vol.63, issue.12, pp.63-1066, 2010.
DOI : 10.1136/jcp.2010.081166

J. H. Paik, Clinicopathologic implication of ALK rearrangement in surgically resected lung cancer A proposal of diagnostic algorithm for ALK-rearranged adenocarcinoma, Lung Cancer, 2011.

D. W. Wong, The EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS. Cancer, pp.115-1723, 2009.

K. Naoki, The PCR-invader method (structure-specific 5??? nuclease-based method), a sensitive method for detecting EGFR gene mutations in lung cancer specimens; comparison with direct sequencing, International Journal of Clinical Oncology, vol.362, issue.1???2, pp.335-379, 2011.
DOI : 10.1056/NEJMoa0909530

S. J. Rodig, Unique Clinicopathologic Features Characterize ALK-Rearranged Lung Adenocarcinoma in the Western Population, Clinical Cancer Research, vol.15, issue.16, pp.15-5216, 2009.
DOI : 10.1158/1078-0432.CCR-09-0802

S. H. Ou, Activity of Crizotinib (PF02341066), a Dual Mesenchymal-Epithelial Transition (MET) and Anaplastic Lymphoma Kinase (ALK) Inhibitor, in a Non-small Cell Lung Cancer Patient with De Novo MET Amplification, Journal of Thoracic Oncology, vol.6, issue.5, pp.942-948, 2011.
DOI : 10.1097/JTO.0b013e31821528d3

T. Sasaki, The biology and treatment of EML4-ALK non-small cell lung cancer, European Journal of Cancer, vol.46, issue.10
DOI : 10.1016/j.ejca.2010.04.002

D. B. Costa, Effects of Erlotinib in EGFR Mutated Non-Small Cell Lung Cancers with Resistance to Gefitinib, Clinical Cancer Research, vol.14, issue.21, pp.14-7060, 2008.
DOI : 10.1158/1078-0432.CCR-08-1455

J. P. Eder, Novel Therapeutic Inhibitors of the c-Met Signaling Pathway in Cancer, Clinical Cancer Research, vol.15, issue.7, pp.2207-2221, 2009.
DOI : 10.1158/1078-0432.CCR-08-1306

J. S. Lee, K. Park, K. S. Lee, D. H. Kim, H. T. Ham et al., al, a randomized phase III study of gefitinib (Iressa) versus standard chemotherapy (gemcitabine plus cisplatin) as a first line treatment fir never-smokers with advanced or metastatic adenocarcinoma of the lung, J Thorac Oncol, vol.1, issue.49, pp.283-287, 2009.

T. Mitsudomi, Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial, The Lancet Oncology, vol.11, issue.2, pp.121-129, 2009.
DOI : 10.1016/S1470-2045(09)70364-X

M. Maemondo, Gefitinib or Chemotherapy for Non???Small-Cell Lung Cancer with Mutated EGFR, New England Journal of Medicine, vol.362, issue.25, pp.362-2380, 2010.
DOI : 10.1056/NEJMoa0909530

C. Zhou, Act Mut+) advanced non-small cell lung cancer (NSCLC)., Journal of Clinical Oncology, vol.29, issue.15_suppl, p.29, 2011.
DOI : 10.1200/jco.2011.29.15_suppl.7520

R. Rosell, Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial, The Lancet Oncology, vol.13, issue.3, pp.13-239, 2012.
DOI : 10.1016/S1470-2045(11)70393-X

W. Brugger, Prospective molecular marker analyses of EGFR and KRAS from a randomized, placebo-controlled study of erlotinib maintenance therapy in advanced non-small-cell lung cancer, J Clin Oncol, issue.31, pp.29-4113, 2011.

G. R. Oxnard, Acquired resistance to EGFR tyrosine kinase inhibitors in EGFRmutant lung cancer: distinct natural history of patients with tumors harboring the T790M mutation, Clin Cancer Res, issue.6, pp.17-1616, 2010.

. Macherey-nagel, Genomic DNA from forensic samples (User manual) NucleoMag 96 Trace, 2006.

T. Bienvenu, [Different procedures for the isolation of DNA from blood samples], Ann Biol Clin, vol.57, issue.1, pp.77-84, 1999.

Q. Pan, W. Pao, and M. Ladanyi, Rapid Polymerase Chain Reaction-Based Detection of Epidermal Growth Factor Receptor Gene Mutations in Lung Adenocarcinomas, The Journal of Molecular Diagnostics, vol.7, issue.3, pp.396-403, 2005.
DOI : 10.1016/S1525-1578(10)60569-7

Z. Su, A Platform for Rapid Detection of Multiple Oncogenic Mutations With Relevance to Targeted Therapy in Non???Small-Cell Lung Cancer, The Journal of Molecular Diagnostics, vol.13, issue.1, pp.74-84, 2011.
DOI : 10.1016/j.jmoldx.2010.11.010

C. D. Hurst, A SNaPshot assay for the rapid and simple detection of four common hotspot codon mutations in the PIK3CA gene, BMC Research Notes, vol.2, issue.1, p.66, 2009.
DOI : 10.1186/1756-0500-2-66

. Key, Immunochemical staining methods, 2001.

A. Didelot, Competitive allele specific TaqMan PCR for KRAS, BRAF and EGFR mutation detection in clinical formalin fixed paraffin embedded samples, Experimental and Molecular Pathology, vol.92, issue.3, pp.92-275, 2012.
DOI : 10.1016/j.yexmp.2012.03.001

J. R. Landis and G. G. Koch, The Measurement of Observer Agreement for Categorical Data, Biometrics, vol.33, issue.1, pp.159-74, 1977.
DOI : 10.2307/2529310

F. Duffaud and P. Therasse, [New guidelines to evaluate the response to treatment in solid tumors], Bull Cancer, vol.87, issue.12, pp.881-887, 2000.

. Inca, Synthèse de l'activité des plateformes hospitalières de génétique moléculaire des cancers en 2010. . Collection Rapports & synthèses, ouvrage collectif édité par l, 2010.

©. Inca, Les tests de génétique moléculaire pour l'accès aux thérapies ciblées. Collection Rapports & synthèses, ouvrage collectif édité par l, 2011.