L. Un-score and . Élevé, 13) présentaient une stabilisation ou une progression de la maladie sous traitement, Le tableau 11 résume les qualités de classement des 45 patients inclus dans cette étude en fonction de leur statut KRAS (tableau 11A) ou de la combinaison du statut KRAS et du score LDA (tableau 11B), p.9

T. Byers, Two Decades of Declining Cancer Mortality: Progress with Disparity, Annual Review of Public Health, vol.31, issue.1, pp.121-153, 2010.
DOI : 10.1146/annurev.publhealth.121208.131047

C. Sawyers, The cancer biomarker problem, Nature, vol.353, issue.7187, pp.548-52, 2008.
DOI : 10.1038/nm1107-1276b

D. Hanahan and R. Weinberg, The hallmarks of cancer. Cell, Jan, vol.7100, issue.1, pp.57-70, 2000.

D. Hanahan and R. Weinberg, Hallmarks of cancer: the next generation. Cell, pp.646-74, 2011.

P. Blume-jensen and T. Hunter, Oncogenic kinase signalling, Nature. May, vol.17411, issue.6835, pp.355-65, 2001.

P. Hubert, Growth factors of the EGF family and their receptors], Bull Cancer, vol.94, issue.7, pp.137-182, 2007.

A. Singh and R. Harris, Autocrine, paracrine and juxtacrine signaling by EGFR ligands. Cell Signal, pp.1183-93, 2005.

T. Holbro and N. Hynes, : Directing Key Signaling Networks Throughout Life, Annual Review of Pharmacology and Toxicology, vol.44, issue.1, pp.195-217, 2004.
DOI : 10.1146/annurev.pharmtox.44.101802.121440

D. Azria and J. Spano, Thérapies ciblées en cancérologie: Libbey Eurotext 10. Sergina NV, Moasser MM. The HER family and cancer: emerging molecular mechanisms and therapeutic targets, Trends Mol Med, vol.13, issue.12, pp.527-561, 2006.

W. Cai, G. Niu, and X. Chen, Multimodality imaging of the HER-kinase axis in cancer, European Journal of Nuclear Medicine and Molecular Imaging, vol.9, issue.Pt 11, pp.186-208, 2008.
DOI : 10.1259/bjr.75.suppl_9.750024

D. Amin, M. Campbell, and M. Moasser, The role of HER3, the unpretentious member of the HER family, in cancer biology and cancer therapeutics, Seminars in Cell & Developmental Biology, vol.21, issue.9, 2010.
DOI : 10.1016/j.semcdb.2010.08.007

M. Wieduwilt, M. Moasser, T. Holbro, G. Civenni, and N. Hynes, The epidermal growth factor receptor family: biology driving targeted therapeutics The ErbB receptors and their role in cancer progression, Cell Mol Life Sci Exp Cell Res, vol.65284, issue.141, pp.1566-8499, 2003.

J. Robert, J. Signalisation-cellulaire-et-cancer-garcia-saenz, J. Sastre, D. Garcia, and E. , 16. Kataoka H. EGFR ligands and their signaling scissors, ADAMs, as new molecular targets for anticancer treatments Biomarkers and anti-EGFR therapies for KRAS wild-type metastatic colorectal cancer, J Dermatol Sci. Clin Transl Oncol, vol.5611, issue.1711, pp.148-53737, 2009.
URL : https://hal.archives-ouvertes.fr/hal-00785035

A. Gschwind, O. Fischer, and A. Ullrich, Metalloprotease-mediated ligand release regulates autocrine signaling through the epidermal growth factor receptor The discovery of receptor tyrosine kinases: targets for cancer therapy, Proc Natl Acad Sci Nat Rev Cancer, vol.964, issue.115, pp.6235-40361, 1999.

B. Gusterson, K. Hunter, R. Bianco, T. Gelardi, V. Damiano et al., Should we be surprised at the paucity of response to EGFR inhibitors? Lancet Oncol Mechanisms of resistance to EGFR inhibitors, Targeted Oncology, vol.102, issue.211, pp.522-731, 2007.

K. Spindler, D. Olsen, J. Nielsen, I. Brandslund, H. Poulsen et al., Epidermal growth factor receptor and epidermal growth factor receptor variant III gene expression in metastatic colorectal cancer Clin Colorectal Cancer, of the type III epidermal growth factor receptor mutation in colorectal cancer, pp.214-222, 2006.

Z. Weihua, R. Tsan, W. Huang, Q. Wu, C. Chiu et al., Survival of Cancer Cells Is Maintained by EGFR Independent of Its Kinase Activity, Cancer Cell, vol.13, issue.5, 2008.
DOI : 10.1016/j.ccr.2008.03.015

J. Schlessinger, Ligand-induced, receptor-mediated dimerization and activation of EGF receptor. Cell, pp.669-72, 2002.

F. Ozcan, P. Klein, M. Lemmon, I. Lax, and J. Schlessinger, Signal transduction by epidermal growth factor occurs through the subclass of high affinity receptors On the nature of low-and high-affinity EGF receptors on living cells, J Cell Biol Proc Natl Acad Sci, vol.109103, issue.2715, pp.2495-5075735, 1989.

T. Ringerike, E. Stang, L. Johannessen, D. Sandnes, F. Levy et al., Highaffinity binding of epidermal growth factor (EGF) to EGF receptor is disrupted by overexpression of mutant dynamin (K44A) High-and low-affinity epidermal growth factor receptor-ligand interactions activate distinct signaling pathways, ):e15945. 30. Sako Y, Minoghchi S, Yanagida T. Single-molecule imaging of EGFR signalling on the surface of living cells, pp.16639-42168, 1998.

G. Liccardi, J. Hartley, and D. Hochhauser, EGFR nuclear translocation modulates DNA repair following cisplatin and ionizing radiation treatment, Cancer Res Feb, vol.171, issue.3, pp.1103-1117, 2011.

H. Lo and M. Hung, Nuclear EGFR signalling network in cancers: linking EGFR pathway to cell cycle progression, nitric oxide pathway and patient survival, British Journal of Cancer, vol.258, issue.2, pp.16-20, 2007.
DOI : 10.1006/excr.2000.4905

H. Lo, Nuclear mode of the EGFR signaling network: biology, prognostic value, and therapeutic implications, Discov Med, vol.10, issue.50, pp.44-51, 2010.

H. Lo, W. Xia, Y. Wei, M. Ali-seyed, S. Huang et al., Novel prognostic value of nuclear epidermal growth factor receptor in breast cancer. Cancer Res [EGFR expression in colorectal cancer and role in tumorigenesis]. Bull Cancer, pp.338-386, 2005.

J. C. Baselga, Y. Chae, and J. Lee, Targeting the epidermal growth factor receptor: a clinical reality Targeting epidermal growth factor receptor in head and neck cancer: lessons learned from cetuximab, J Clin Oncol Exp Biol Med, vol.19, issue.37, pp.41-45, 2001.

B. Voldborg, L. Damstrup, M. Spang-thomsen, H. Poulsen, G. Pines et al., Epidermal growth factor receptor (EGFR) and EGFR mutations, function and possible role in clinical trials Oncogenic mutant forms of EGFR: lessons in signal transduction and targets for cancer therapy Current situation of Panitumumab, Matuzumab, Nimotuzumab and Zalutumumab Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry, Ann Oncol. FEBS Lett. Jun Acta Oncol. J Clin Oncol, vol.85844723, issue.419, pp.1197-2062699, 1997.

O. Dassonville, J. Formento, M. Francoual, A. Ramaioli, J. Santini et al., Expression of epidermal growth factor receptor and survival in upper aerodigestive tract cancer., Journal of Clinical Oncology, vol.11, issue.10, pp.1873-1881, 1993.
DOI : 10.1200/JCO.1993.11.10.1873

R. Hitt, E. Ciruelos, M. Amador, A. Benito, J. Sanchez et al., Prognostic value of the epidermal growth factor receptor (EGRF) and p53 in advanced head and neck squamous cell carcinoma patients treated with induction chemotherapy, European Journal of Cancer, vol.41, issue.3, 2005.
DOI : 10.1016/j.ejca.2004.10.014

B. Luber, S. Lorenzen, S. Hegewisch-becker, G. Folprecht, and E. Woll, Phase II trial of erlotinib in gastroesophageal junction and gastric adenocarcinomas: SWOG 0127, J Clin Oncol, vol.24, issue.30, 2006.

J. Giltnane, L. Ryden, M. Cregger, P. Bendahl, K. Jirstrom et al., Quantitative Measurement of Epidermal Growth Factor Receptor Is a Negative Predictive Factor for Tamoxifen Response in Hormone Receptor???Positive Premenopausal Breast Cancer, Journal of Clinical Oncology, vol.25, issue.21, pp.3007-3021, 2007.
DOI : 10.1200/JCO.2006.08.9938

D. Cohen, B. Lane, J. T. Magi-galluzzi, C. Finke, J. Rini et al., The Prognostic Significance of Epidermal Growth Factor Receptor Expressionin Clear-Cell Renal Cell Carcinoma: A Call for Standardized Methods for Immunohistochemical Evaluation, Clinical Genitourinary Cancer, vol.5, issue.4, pp.264-70, 2007.
DOI : 10.3816/CGC.2007.n.002

J. Raizer and . Her1, HER1/EGFR tyrosine kinase inhibitors for the treatment of glioblastoma multiforme, Journal of Neuro-Oncology, vol.63, issue.Suppl 7, pp.77-86, 2005.
DOI : 10.1200/JCO.2004.99.242

C. Pelloski, K. Ballman, A. Furth, L. Zhang, E. Lin et al., Epidermal Growth Factor Receptor Variant III Status Defines Clinically Distinct Subtypes of Glioblastoma, Journal of Clinical Oncology, vol.25, issue.16, pp.2288-94, 2007.
DOI : 10.1200/JCO.2006.08.0705

J. Edwards, P. Traynor, A. Munro, C. Pirret, B. Dunne et al., The role of HER1- HER4 and EGFRvIII in hormone-refractory prostate cancer. Clin Cancer Res, pp.123-153, 2006.

S. Bellone, G. Frera, G. Landolfi, C. Romani, E. Bandiera et al., Overexpression of epidermal growth factor type-1 receptor (EGF-R1) in cervical cancer: Implications for Cetuximab-mediated therapy in recurrent/metastatic disease, Gynecologic Oncology, vol.106, issue.3, pp.513-533, 2007.
DOI : 10.1016/j.ygyno.2007.04.028

T. Prickett, N. Agrawal, X. Wei, K. Yates, J. Lin et al., Analysis of the tyrosine kinome in melanoma reveals recurrent mutations in ERBB4, Nature Genetics, vol.18, issue.10, 2009.
DOI : 10.1101/gr.8.3.195

K. Wennerberg, K. Rossman, and C. Der, The Ras superfamily at a glance, Journal of Cell Science, vol.118, issue.5, pp.843-849, 2005.
DOI : 10.1242/jcs.01660

C. Pratilas, D. Solit, G. Wink, and C. Mattos, Targeting the mitogen-activated protein kinase pathway: physiological feedback and drug response Clin Cancer Res Transformation efficiency of RasQ61 mutants linked to structural features of the switch regions in the presence of Raf, Structure, vol.16, issue.13, pp.3329-3363, 2007.

M. Raman, W. Chen, and M. Cobb, Differential regulation and properties of MAPKs, Oncogene, vol.24, issue.22
DOI : 10.1016/j.str.2006.04.006

S. Wang, R. Ghosh, and S. Chellappan, Raf-1 Physically Interacts with Rb and Regulates Its Function: a Link between Mitogenic Signaling and Cell Cycle Regulation, Molecular and Cellular Biology, vol.18, issue.12, 1998.
DOI : 10.1128/MCB.18.12.7487

M. Phosphorylation-by and R. , and mitogen-activated protein kinase: analysis of phosphopeptides and regulation of activity 63. Ramos JW. The regulation of extracellular signal-regulated kinase (ERK) in mammalian cells, Mol Biol Cell Feb Int J Biochem Cell Biol, vol.540, issue.212, pp.193-2012707, 1994.

B. Jiang and L. Liu, PI3K/PTEN signaling in tumorigenesis and angiogenesis, Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, vol.1784, issue.1, pp.19-65, 2009.
DOI : 10.1016/j.bbapap.2007.09.008

J. Engelman, A. Bellacosa, C. Kumar, D. Cristofano, A. Testa et al., Targeting PI3K signalling in cancer: opportunities, challenges and limitations Activation of AKT kinases in cancer: implications for therapeutic targeting, Nat Rev Cancer. Adv Cancer Res, vol.994, issue.66, pp.550-6229, 2005.

W. Shen, A. Balajee, J. Wang, H. Wu, C. Eng et al., Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell Novel agents on the horizon for cancer therapy, Thérapies moléculaires ciblées -De la biologie aux applications, pp.157-70111, 2007.

K. Imai, A. Takaoka, F. Bibeau, E. Lopez-crapez, D. Fiore et al., Comparing antibody and small-molecule therapies for cancer Impact of Fc{gamma}RIIa-Fc{gamma}RIIIa polymorphisms and KRAS mutations on the clinical outcome of patients with metastatic colorectal cancer treated with cetuximab plus irinotecan Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases downregulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors, Nat Rev Cancer. J Clin Oncol. Mar Am J Pathol, vol.627, issue.72, pp.714-271122, 1997.

D. Wheeler, E. Dunn, and P. Harari, Understanding resistance to EGFR inhibitors???impact on future treatment strategies, Nature Reviews Clinical Oncology, vol.6, issue.9, pp.493-507, 2010.
DOI : 10.1091/mbc.4.1.121

C. Oldenhuis, S. Oosting, J. Gietema, and E. De-vries, Prognostic versus predictive value of biomarkers in oncology, European Journal of Cancer, vol.44, issue.7, pp.946-53, 2008.
DOI : 10.1016/j.ejca.2008.03.006

D. Sargent, B. Conley, A. C. Collette, L. Dicato, M. Arber et al., Clinical Trial Designs for Predictive Marker Validation in Cancer Treatment Trials, Journal of Clinical Oncology, vol.23, issue.9, pp.2020-2027, 2005.
DOI : 10.1200/JCO.2005.01.112

M. Buyse, N. Meropol, P. Loehrer, . Sr, M. Needle et al., Statistical issues in identifying, validating, and using molecular markers in clinical trials ESMO -Impakt Breast cancer conference Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor, J Clin Oncol, vol.22, issue.7, pp.1201-1209, 2004.

M. Hebbar, A. Wacrenier, C. Desauw, O. Romano, S. Cattan et al., Lack of usefulness of epidermal growth factor receptor expression determination for cetuximab therapy in patients with colorectal cancer Anticancer Drugs Lack of correlation between epidermal growth factor receptor status and response to Panitumumab monotherapy in metastatic colorectal cancer Clin Cancer Res Determinants of tumor response and survival with erlotinib in patients with non--small-cell lung cancer Analysis of epidermal growth factor receptor expression as a predictive factor for response to gefitinib ('Iressa', ZD1839) in non-small-cell lung cancer al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab, J Clin Oncol Aug Br J Cancer J Clin Oncol, vol.1716229126, issue.863, pp.855-72205, 2004.

M. Krause, M. Baumann, P. Laurent-puig, A. Cayre, G. Manceau et al., Clinical biomarkers of kinase activity: examples from EGFR inhibition trials Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer, Cancer Metastasis Rev. J Clin Oncol, vol.2727, issue.8835, pp.387-4025924, 2008.

M. Moroni, S. Veronese, S. Benvenuti, G. Marrapese, A. Sartore-bianchi et al., Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study, The Lancet Oncology, vol.6, issue.5, pp.279-86, 2005.
DOI : 10.1016/S1470-2045(05)70102-9

A. Lievre, J. Bachet, L. Corre, D. Boige, V. Landi et al., KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer, Cancer Res, 2006.

A. Sartore-bianchi, M. Moroni, S. Veronese, C. Carnaghi, E. Bajetta et al., Epidermal Growth Factor Receptor Gene Copy Number and Clinical Outcome of Metastatic Colorectal Cancer Treated With Panitumumab, Journal of Clinical Oncology, vol.25, issue.22, pp.3238-3283, 2007.
DOI : 10.1200/JCO.2007.11.5956

M. Frattini, P. Saletti, E. Romagnani, V. Martin, F. Molinari et al., PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients, British Journal of Cancer, vol.24, issue.8, pp.1139-1184, 2007.
DOI : 10.1016/j.ctrv.2003.10.003

N. Personeni, S. Fieuws, H. Piessevaux, D. Hertogh, G. et al., Clinical Usefulness of EGFR Gene Copy Number as a Predictive Marker in Colorectal Cancer Patients Treated with Cetuximab: A Fluorescent In situ Hybridization Study, Clinical Cancer Research, vol.14, issue.18, pp.5869-76, 2008.
DOI : 10.1158/1078-0432.CCR-08-0449

F. Cappuzzo, G. Finocchiaro, E. Rossi, P. Janne, C. Carnaghi et al., EGFR FISH assay predicts for response to cetuximab in chemotherapy refractory colorectal cancer patients Ann Oncol A polymorphism of EGFR extracellular domain is associated with progression free-survival in metastatic colorectal cancer patients receiving cetuximab-based treatment, BMC Cancer, vol.198, issue.4, pp.717-23169, 2008.

S. Richman, G. Hutchins, M. Seymour, and P. Quirke, -ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab What can the molecular pathologist offer for optimal decision making? Ann Oncol, J Clin Oncol, vol.2521, issue.99, pp.3230-3237, 2007.

A. Chopra, 2-amino-3-(4-isothiocyanatophenyl)propyl]-trans- (S,S)-cyclohexane-1,2 -diamine-pentaacetic acid (CHX-A''-DTPA) conjugated monoclonal antibody L8A4 against epidermal growth factor receptor variant III (EGFRvIII) Molecular Imaging & Contrast Agent Database, 2010.

J. Sok, F. Coppelli, S. Thomas, M. Lango, S. Xi et al., Mutant epidermal growth factor receptor (EGFRvIII) contributes to head and neck cancer growth and resistance to EGFR targeting. Clin Cancer Res, pp.5064-73, 2006.

D. Fiore, F. Sesboue, R. Michel, P. Sabourin, J. Frebourg et al., Molecular determinants of anti-EGFR sensitivity and resistance in metastatic colorectal cancer, British Journal of Cancer, vol.25, issue.12, pp.1765-72, 2010.
DOI : 10.4161/cc.6.9.4211

A. Lievre, H. Blons, and P. Laurent-puig, Oncogenic mutations as predictive factors in colorectal cancer, Oncogene, vol.15, issue.21, pp.3033-3076, 2010.
DOI : 10.1016/S0002-9440(10)65579-4

E. Fearon and B. Vogelstein, A genetic model for colorectal tumorigenesis. Cell, 1990.

T. Pretlow, T. Brasitus, N. Fulton, C. Cheyer, and E. Kaplan, K-ras Mutations in Putative Preneoplastic Lesions in Human Colon, JNCI Journal of the National Cancer Institute, vol.85, issue.24, pp.2004-2011, 1993.
DOI : 10.1093/jnci/85.24.2004

M. Fujita, T. Enomoto, M. Inoue, O. Tanizawa, M. Ozaki et al., Activation and More Frequently in Serous Adenocarcinomas than in Other Common Epithelial Tumors of the Human Ovary, Japanese Journal of Cancer Research, vol.7, issue.13, pp.1247-56, 1994.
DOI : 10.1038/355846a0

R. Amado, M. Wolf, M. Peeters, E. Van-cutsem, S. Siena et al., Is Required for Panitumumab Efficacy in Patients With Metastatic Colorectal Cancer, Journal of Clinical Oncology, vol.26, issue.10, pp.1626-1660, 2008.
DOI : 10.1200/JCO.2007.14.7116

S. Benvenuti, A. Sartore-bianchi, D. Nicolantonio, F. Zanon, C. Moroni et al., Oncogenic Activation of the RAS/RAF Signaling Pathway Impairs the Response of Metastatic Colorectal Cancers to Anti-Epidermal Growth Factor Receptor Antibody Therapies, Cancer Research, vol.67, issue.6, pp.2643-2651, 2007.
DOI : 10.1158/0008-5472.CAN-06-4158

W. De-roock, H. Piessevaux, D. Schutter, J. Janssens, M. et al., KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab, Annals of Oncology, vol.90, issue.3, pp.508-523, 2008.
DOI : 10.1093/jnci/90.9.675

D. Fiore, F. Blanchard, F. Charbonnier, F. , L. Pessot et al., Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy, British Journal of Cancer, vol.14, issue.8, pp.1166-1175, 2007.
DOI : 10.1093/jnci/92.3.205

E. Van-custem, A meta-analysis of the CRYSTAL and OPUS studies combining cetuximab with chemotherapy (CT) as 1stline treatment for patients (pts) with metastatic colorectal cancer (mCRC): results according to KRAS and BRAF mutation status, Eur J Cancer, vol.7, p.345, 2009.

C. Bokemeyer, I. Bondarenko, J. Hartmann, D. Braud, F. Schuch et al., Cetuximab plus 5-FU/FA/oxaliplatin (FOLFOX-4) versus FOLFOX-4 in the first-line treatment of metastatic colorectal cancer (mCRC): OPUS, a randomised phase II study, J Clin Oncol, vol.25172, 2007.

H. Linardou, I. Dahabreh, D. Kanaloupiti, F. Siannis, D. Bafaloukos et al., 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

S. Edkins, O. Meara, S. Parker, A. Stevens, C. Reis et al., Recurrent KRAS codon 146 mutations in human colorectal cancer, Cancer Biology & Therapy, vol.5, issue.8, pp.928-960, 2006.
DOI : 10.4161/cbt.5.8.3251

W. De-roock, B. Claes, D. Bernasconi, D. Schutter, J. Biesmans et al., Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis, The Lancet Oncology, vol.11, issue.8, pp.753-62, 2010.
DOI : 10.1016/S1470-2045(10)70130-3

F. Loupakis, A. Ruzzo, C. Cremolini, B. Vincenzi, L. Salvatore et al., KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer, British Journal of Cancer, vol.8, issue.4, pp.715-736, 2009.
DOI : 10.1038/onc.2008.335

A. Sartore-bianchi, K. Bencardino, D. Nicolantonio, F. Pozzi, F. Funaioli et al., Integrated molecular dissection of the epidermal growth factor receptor (EFGR) oncogenic pathway to predict response to EGFR-targeted monoclonal antibodies in metastatic colorectal cancer, Targeted Oncology, vol.27, issue.30, pp.19-28, 2010.
DOI : 10.1007/s11523-010-0138-5

C. Mao, R. Liao, L. Qiu, X. Wang, H. Ding et al., BRAF V600E mutation and resistance to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer: a meta-analysis, Molecular Biology Reports, vol.2, issue.4, pp.2219-2242, 2011.
DOI : 10.1038/35052073

A. Russo, S. Rizzo, G. Bronte, N. Silvestris, G. Colucci et al., The Long and Winding Road to Useful Predictive Factors for Anti-EGFR Therapy in Metastatic Colorectal Carcinoma: The KRAS/BRAF Pathway, Oncology, vol.77, issue.1, pp.57-68, 2009.
DOI : 10.1159/000258497

A. Lievre, E. Rouleau, B. Buecher, and E. Mitry, Clinical significance of BRAF mutations in colorectal cancer]. Bull Cancer, pp.1441-52, 2010.

D. Nicolantonio, F. Martini, M. Molinari, F. Sartore-bianchi, A. Arena et al., Is Required for Response to Panitumumab or Cetuximab in Metastatic Colorectal Cancer, Journal of Clinical Oncology, vol.26, issue.35, pp.5705-5717, 2008.
DOI : 10.1200/JCO.2008.18.0786

N. Normanno, S. Tejpar, and F. Ciardiello, Re: Biomarkers Predicting Clinical Outcome of Epidermal Growth Factor Receptor-Targeted Therapy in Metastatic Colorectal Cancer, JNCI Journal of the National Cancer Institute, vol.7, issue.11, pp.573-578, 2010.
DOI : 10.1056/NEJMra0707704

S. Siena, A. Sartore-bianchi, D. Nicolantonio, F. Balfour, J. Bardelli et al., Response: Re: Biomarkers Predicting Clinical Outcome of Epidermal Growth Factor Receptor-Targeted Therapy in Metastatic Colorectal Cancer, JNCI Journal of the National Cancer Institute, vol.4, issue.10, pp.573-578, 2010.
DOI : 10.1371/journal.pone.0007287

J. Souglakos, J. Philips, R. Wang, S. Marwah, M. Silver et al., Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer, British Journal of Cancer, vol.62, issue.3, pp.465-72, 2009.
DOI : 10.1126/science.1145720

A. Bardelli and S. Siena, Molecular Mechanisms of Resistance to Cetuximab and Panitumumab in Colorectal Cancer, Journal of Clinical Oncology, vol.28, issue.7, pp.1254-61, 2010.
DOI : 10.1200/JCO.2009.24.6116

S. Kim, J. Kim, J. Kim, C. Yun, E. Kim et al., Acquired resistance to cetuximab is mediated by increased PTEN instability and leads cross-resistance to gefitinib in HCC827 NSCLC cells, Cancer Letters, vol.296, issue.2, pp.150-159, 2010.
DOI : 10.1016/j.canlet.2010.04.006

S. Ogino, K. Nosho, G. Kirkner, K. Shima, N. Irahara et al., Mutation Is Associated With Poor Prognosis Among Patients With Curatively Resected Colon Cancer, Journal of Clinical Oncology, vol.27, issue.9, pp.1477-84, 2009.
DOI : 10.1200/JCO.2008.18.6544

A. Sartore-bianchi, M. Martini, F. Molinari, S. Veronese, M. Nichelatti et al., PIK3CA Mutations in Colorectal Cancer Are Associated with Clinical Resistance to EGFR-Targeted Monoclonal Antibodies, Cancer Research, vol.69, issue.5, pp.1851-1858, 2009.
DOI : 10.1158/0008-5472.CAN-08-2466

P. Cairns, K. Okami, S. Halachmi, N. Halachmi, M. Esteller et al., Frequent inactivation of PTEN/MMAC1 in primary prostate cancer. Cancer Res, pp.4997-5000, 1997.

H. Feilotter, M. Nagai, A. Boag, C. Eng, and L. Mulligan, Analysis of PTEN and the 10q23 region in primary prostate carcinomas. Oncogene, pp.1743-1751, 1998.

Y. Whang, X. Wu, H. Suzuki, R. Reiter, C. Tran et al., Inactivation of the tumor suppressor PTEN/MMAC1 in advanced human prostate cancer through loss of expression, Proceedings of the National Academy of Sciences, vol.94, issue.17, pp.5246-50, 1998.
DOI : 10.1073/pnas.94.17.9052

P. Guldberg, P. Thor-straten, A. Birck, V. Ahrenkiel, A. Kirkin et al., Disruption of the MMAC1/PTEN gene by deletion or mutation is a frequent event in malignant melanoma, Cancer Res, vol.57, issue.17, pp.3660-3663, 1997.

K. Gronbaek, J. Zeuthen, P. Guldberg, E. Ralfkiaer, and K. Hou-jensen, Alterations of the MMAC1/PTEN gene in lymphoid malignancies, Blood, vol.91, issue.11, pp.4388-90, 1998.

A. Perren, L. Weng, A. Boag, U. Ziebold, K. Thakore et al., Immunohistochemical Evidence of Loss of PTEN Expression in Primary Ductal Adenocarcinomas of the Breast, The American Journal of Pathology, vol.155, issue.4, pp.1253-60, 1999.
DOI : 10.1016/S0002-9440(10)65227-3

N. Nassif, G. Lobo, X. Wu, C. Henderson, C. Morrison et al., PTEN mutations are common in sporadic microsatellite stable colorectal cancer. Oncogene, pp.617-645, 2004.

Y. Nagata, K. Lan, X. Zhou, M. Tan, F. Esteva et al., PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell, pp.117-144, 2004.

B. Dave, I. Migliaccio, M. Gutierrez, M. Wu, G. Chamness et al., Loss of Phosphatase and Tensin Homolog or Phosphoinositol-3 Kinase Activation and Response to Trastuzumab or Lapatinib in Human Epidermal Growth Factor Receptor 2???Overexpressing Locally Advanced Breast Cancers, Journal of Clinical Oncology, vol.29, issue.2, pp.166-73, 2010.
DOI : 10.1200/JCO.2009.27.7814

D. Wheeler, S. Huang, T. Kruser, M. Nechrebecki, E. Armstrong et al., Mechanisms of acquired resistance to cetuximab: role of HER (ErbB) family members, Oncogene, vol.10, issue.28, pp.3944-56, 2008.
DOI : 10.4161/cbt.5.10.3226

F. Cappuzzo, M. Varella-garcia, G. Finocchiaro, M. Skokan, S. Gajapathy et al., Primary resistance to cetuximab therapy in EGFR FISH-positive colorectal cancer patients, British Journal of Cancer, vol.57, issue.1, pp.83-92, 2008.
DOI : 10.1002/cncr.10945

T. Winder, W. Zhang, D. Yang, Y. Ning, P. Bohanes et al., Germline polymorphisms in genes involved in the IGF1 pathway predict efficacy of cetuximab in wildtype KRAS mCRC patients. Clin Cancer Res, pp.5591-602, 2010.

Y. Tao, V. Pinzi, J. Bourhis, and E. Deutsch, Mechanisms of Disease: signaling of the insulin-like growth factor 1 receptor pathway???therapeutic perspectives in cancer, Nature Clinical Practice Oncology, vol.48, issue.10, pp.591-602, 2007.
DOI : 10.1093/jnci/94.14.1099

A. Oden-gangloff, D. Fiore, F. Bibeau, F. Lamy, A. Bougeard et al., TP53 mutations predict disease control in metastatic colorectal cancer treated with cetuximab-based chemotherapy, British Journal of Cancer, vol.97, issue.8, pp.1330-1335, 2009.
DOI : 10.1200/JCO.2005.04.096

B. Jacobs, D. Roock, W. Piessevaux, H. , V. Oirbeek et al., Amphiregulin and Epiregulin mRNA Expression in Primary Tumors Predicts Outcome in Metastatic Colorectal Cancer Treated With Cetuximab, Journal of Clinical Oncology, vol.27, issue.30, pp.5068-74, 2009.
DOI : 10.1200/JCO.2008.21.3744

S. Siena, A. Sartore-bianchi, D. Nicolantonio, F. Balfour, J. Bardelli et al., Biomarkers Predicting Clinical Outcome of Epidermal Growth Factor Receptor???Targeted Therapy in Metastatic Colorectal Cancer, JNCI: Journal of the National Cancer Institute, vol.27, issue.28, pp.1308-1332, 2009.
DOI : 10.1038/onc.2008.19

A. Lopez-albaitero and R. Ferris, Immune Activation by Epidermal Growth Factor Receptor???Specific Monoclonal Antibody Therapy for Head and Neck Cancer, Archives of Otolaryngology???Head & Neck Surgery, vol.133, issue.12, pp.1277-81, 2007.
DOI : 10.1001/archotol.133.12.1277

D. Paez, L. Pare, I. Espinosa, J. Salazar, E. Del-rio et al., Immunoglobulin G fragment C receptor polymorphisms and KRAS mutations: Are they useful biomarkers of clinical outcome in advanced colorectal cancer treated with anti-EGFR-based therapy?, Cancer Science, vol.24, issue.9, pp.2048-53, 2010.
DOI : 10.1111/j.1349-7006.2010.01621.x

F. Ciardiello, R. Bianco, R. Caputo, R. Caputo, V. Damiano et al., Antitumor Activity of ZD6474, a Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor, in Human Cancer Cells with Acquired Resistance to Antiepidermal Growth Factor Receptor Therapy, Clinical Cancer Research, vol.10, issue.2, pp.784-93, 2004.
DOI : 10.1158/1078-0432.CCR-1100-03

D. Vallbohmer, W. Zhang, M. Gordon, D. Yang, Y. J. Press et al., Molecular Determinants of Cetuximab Efficacy, Journal of Clinical Oncology, vol.23, issue.15, pp.3536-3580, 2005.
DOI : 10.1200/JCO.2005.09.100

A. Lievre and P. Laurent-puig, Predictive factors of response to anti-EGFR treatments in colorectal cancer]. Bull Cancer, pp.133-173, 2008.

S. Tejpar, M. Peeters, Y. Humblet, H. Gelderblom, J. Vermorken et al., Phase I/II study of cetuximab dose-escalation in patients with metastatic colorectal cancer with no or slight skin reactions on cetuximab standard dose treatment (Everest) : pharmacokinetic, pharmacodynamic and efficacy data, Proc Am Soc Clin Oncol, vol.25, p.4037, 2007.

R. Sipples, Common Side Effects of Anti-EGFR Therapy: Acneform Rash, Seminars in Oncology Nursing, vol.22, issue.1, pp.28-34, 2006.
DOI : 10.1016/j.soncn.2006.01.013

J. Ludwig and J. Weinstein, Biomarkers in Cancer Staging, Prognosis and Treatment Selection, Nature Reviews Cancer, vol.2, issue.Suppl. 8, pp.845-56, 2005.
DOI : 10.1016/S1471-4892(02)00185-6

S. Mandrekar and D. Sargent, Clinical Trial Designs for Predictive Biomarker Validation: Theoretical Considerations and Practical Challenges, Journal of Clinical Oncology, vol.27, issue.24, pp.4027-4061, 2009.
DOI : 10.1200/JCO.2009.22.3701

B. Freidlin and R. Simon, Adaptive Signature Design: An Adaptive Clinical Trial Design for Generating and Prospectively Testing A Gene Expression Signature for Sensitive Patients, Clinical Cancer Research, vol.11, issue.21, pp.7872-7880, 2005.
DOI : 10.1158/1078-0432.CCR-05-0605

W. Jiang, B. Freidlin, and R. Simon, Biomarker-Adaptive Threshold Design: A Procedure for Evaluating Treatment With Possible Biomarker-Defined Subset Effect, JNCI Journal of the National Cancer Institute, vol.69, issue.10, 2007.
DOI : 10.1056/NEJMoa050736

T. Okano, T. Kondo, K. Fujii, T. Nishimura, T. Takano et al., Proteomic Signature Corresponding to the Response to Gefitinib (Iressa, ZD1839), an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in Lung Adenocarcinoma, Clinical Cancer Research, vol.13, issue.3, pp.799-805, 2007.
DOI : 10.1158/1078-0432.CCR-06-1654

D. Lee, M. Yu, E. Lee, H. Kim, Y. Yang et al., Tumor-specific apoptosis caused by deletion of the ERBB3 pseudo-kinase in mouse intestinal epithelium, Journal of Clinical Investigation, vol.119, issue.9, 2009.
DOI : 10.1172/JCI36435DS1

N. Ferrara, H. Gerber, and J. Lecouter, The biology of VEGF and its receptors, Nature Medicine, vol.99, issue.21, pp.669-76, 2003.
DOI : 10.1073/pnas.152324099

E. Cidon, The Challenge of Metastatic Colorectal Cancer, Clinical Medicine Insights: Oncology, vol.4, pp.55-60, 2010.
DOI : 10.4137/CMO.S5214

. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer, J Clin Oncol Feb, vol.1027, issue.5, pp.663-71, 2009.

D. Jonker, O. Callaghan, C. Karapetis, C. Zalcberg, J. Tu et al., Cetuximab for the Treatment of Colorectal Cancer, New England Journal of Medicine, vol.357, issue.20, pp.2040-2048, 2007.
DOI : 10.1056/NEJMoa071834

X. Yang, X. Jia, J. Corvalan, P. Wang, and C. Davis, Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy, Critical Reviews in Oncology/Hematology, vol.38, issue.1, pp.17-23, 2001.
DOI : 10.1016/S1040-8428(00)00134-7

N. West, M. Dattani, P. Mcshane, G. Hutchins, J. Grabsch et al., The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients, British Journal of Cancer, vol.26, issue.10, pp.1519-1542, 2010.
DOI : 10.1016/j.humpath.2007.04.008

S. Siena, M. Peeters, E. Van-cutsem, Y. Humblet, P. Conte et al., Association of progression-free survival with patient-reported outcomes and survival: results from a randomised phase 3 trial of panitumumab, British Journal of Cancer, vol.59, issue.11, pp.1469-74, 2007.
DOI : 10.1038/35052073

S. Siena, J. Tabernero, D. Cunningham, P. Koralewski, P. Ruff et al., Randomized phase III study of panitumumab (pmab) with FOLFOX4 compared to FOLFOX4 alone as first-line treatment (tx) for metastatic colorectal cancer (mCRC): PRIME trial analysis by epidermal growth factor receptor (EGFR) tumor staining., Journal of Clinical Oncology, vol.28, issue.15_suppl, p.3566, 2010.
DOI : 10.1200/jco.2010.28.15_suppl.3566

M. Peeters, A. Cervantes-ruiperez, A. Strickland, T. Ciuleanu, P. Mainwaring et al., Randomized phase III study of panitumumab (pmab) with FOLFIRI versus FOLFIRI alone as second-line treatment (tx) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis by tumor epidermal growth factor receptor (EGFR) staining., ASCO Annual Meeting, 2010.
DOI : 10.1200/jco.2010.28.15_suppl.3565

M. Fakih and M. Vincent, Adverse events associated with anti-EGFR therapies for the treatment of metastatic colorectal cancer, Current Oncology, vol.17, issue.S1, pp.18-30, 2010.
DOI : 10.3747/co.v17iS1.615

D. Santini, F. Loupakis, B. Vincenzi, I. Floriani, I. Stasi et al., High Concordance of KRAS Status Between Primary Colorectal Tumors and Related Metastatic Sites: Implications for Clinical Practice, The Oncologist, vol.13, issue.12, pp.1270-1275, 2008.
DOI : 10.1634/theoncologist.2008-0181

J. Van-krieken, A. Jung, T. Kirchner, F. Carneiro, R. Seruca et al., KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program. Virchows Arch, pp.417-448, 2008.

N. Normanno, S. Tejpar, F. Morgillo, D. Luca, A. Van-cutsem et al., Implications for KRAS status and EGFR-targeted therapies in metastatic CRC, Nature Reviews Clinical Oncology, vol.276, issue.9, pp.519-546, 2009.
DOI : 10.1016/S1525-1578(10)60571-5

C. Kohne, How to integrate molecular targeted agents in the continuum of care, Annals of Oncology, vol.370, issue.9582, pp.134-143, 2010.
DOI : 10.1016/S0140-6736(07)61087-3

S. Kopetz, G. Chang, M. Overman, C. Eng, D. Sargent et al., Improved Survival in Metastatic Colorectal Cancer Is Associated With Adoption of Hepatic Resection and Improved Chemotherapy, Journal of Clinical Oncology, vol.27, issue.22, pp.3677-83, 2009.
DOI : 10.1200/JCO.2008.20.5278

T. Kobunai, T. Watanabe, Y. Yamamoto, and K. Eshima, The frequency of KRAS mutation detection in human colon carcinoma is influenced by the sensitivity of assay methodology: A comparison between direct sequencing and real-time PCR, Biochemical and Biophysical Research Communications, vol.395, issue.1, pp.158-62, 2010.
DOI : 10.1016/j.bbrc.2010.03.167

G. Perkins, A. Lievre, C. Ramacci, T. Meatchi, A. De-reynies et al., Additional value of EGFR downstream signaling phosphoprotein expression to KRAS status for response to anti-EGFR antibodies in colorectal cancer, International Journal of Cancer, vol.67, issue.6, pp.1321-1352, 2010.
DOI : 10.1002/ijc.25152

M. Krypuy, G. Newnham, D. Thomas, M. Conron, and A. Dobrovic, High resolution melting analysis for the rapid and sensitive detection of mutations in clinical samples: KRAS codon 12 and 13 mutations in non-small cell lung cancer, BMC Cancer, vol.52, issue.12, p.295, 2006.
DOI : 10.1373/clinchem.2006.068205

C. Schimanski, U. Linnemann, and M. Berger, Sensitive detection of K-ras mutations augments diagnosis of colorectal cancer metastases in the liver, Cancer Res, vol.59, issue.20, pp.5169-75, 1999.

M. Etienne-grimaldi, J. Formento, M. Francoual, E. Francois, P. Formento et al., K-Ras Mutations and Treatment Outcome in Colorectal Cancer Patients Receiving Exclusive Fluoropyrimidine Therapy, Clinical Cancer Research, vol.14, issue.15, pp.4830-4835, 2008.
DOI : 10.1158/1078-0432.CCR-07-4906

S. Bouali, A. Chretien, C. Ramacci, M. Rouyer, P. Becuwe et al., PTEN expression controls cellular response to cetuximab by mediating PI3K/AKT and RAS/RAF/MAPK downstream signaling in KRAS wild-type, hormone refractory prostate cancer cells, Oncol Rep, vol.21, issue.3, pp.731-736, 2009.

W. Weichert, C. Schewe, A. Lehmann, C. Sers, C. Denkert et al., KRAS Genotyping of Paraffin-Embedded Colorectal Cancer Tissue in Routine Diagnostics, The Journal of Molecular Diagnostics, vol.12, issue.1, pp.35-42, 2010.
DOI : 10.2353/jmoldx.2010.090079

J. Gonzalez-bosquet, J. Calcei, J. Wei, M. Garcia-closas, M. Sherman et al., Detection of Somatic Mutations by High-Resolution DNA Melting (HRM) Analysis in Multiple Cancers, PLoS ONE, vol.1, issue.1, p.14522
DOI : 10.1371/journal.pone.0014522.s005

C. Wittwer, High-resolution DNA melting analysis: advancements and limitations, Human Mutation, vol.64, issue.6
DOI : 10.1002/humu.20951

H. Do, M. Krypuy, P. Mitchell, S. Fox, and A. Dobrovic, High resolution melting analysis for rapid and sensitive EGFR and KRAS mutation detection in formalin fixed paraffin embedded biopsies, BMC Cancer, vol.12, issue.8, p.142, 2008.
DOI : 10.1158/1078-0432.CCR-05-2845

. De, F. Vega, K. Lazaruk, M. Rhodes, and M. Wenz, Assessment of two flexible and compatible SNP genotyping platforms: TaqMan SNP Genotyping Assays and the SNPlex Genotyping System, Mutat Res, vol.573, issue.12, pp.111-146, 2005.

N. Gibson, The use of real-time PCR methods in DNA sequence variation analysis, Clinica Chimica Acta, vol.363, issue.1-2
DOI : 10.1016/j.cccn.2005.06.022

D. Petris and P. , Discovery and validation of protein biomarkers for lung cancer, Thèse, 2010.

W. Fadhil, S. Ibrahem, R. Seth, and M. Ilyas, Quick-multiplex-consensus (QMC)-PCR followed by high-resolution melting: a simple and robust method for mutation detection in formalin-fixed paraffin-embedded tissue, Journal of Clinical Pathology, vol.63, issue.2, pp.134-174, 2010.
DOI : 10.1136/jcp.2009.070508

W. Xia, Y. Wei, Y. Du, J. Liu, C. B. Yu et al., Nuclear expression of epidermal growth factor receptor is a novel prognostic value in patients with ovarian cancer, Molecular Carcinogenesis, vol.12, issue.7, pp.610-617, 2009.
DOI : 10.1177/29.4.6166661

G. Ruiz, M. Floor, K. Rijmen, F. Grunberg, K. Rodriguez et al., EGFR and K-ras mutation analysis in non-small cell lung cancer: comparison of paraffin embedded versus frozen specimens, Cell Oncol, vol.29, issue.3, pp.257-64, 2007.

F. Bibeau, H. Frugier, E. Crapez, P. Lamy, M. Ychou et al., mutation testing in patients with metastatic colorectal carcinoma: An 18-month experience emphasizing the risk of false-negative results., Journal of Clinical Oncology, vol.28, issue.15_suppl, 2010.
DOI : 10.1200/jco.2010.28.15_suppl.3572

S. Tournier, P. Kirzin, and . Brousset, Impact of the amount of tumor cells in tissue samples for detection of KRAS mutations in colorectal cancer, Journal of Clinical Oncology, vol.2010, issue.3571, 2010.

F. Bibeau, H. , E. Crapez, P. Lamy, M. Ychou et al., mutation testing in patients with metastatic colorectal carcinoma: An 18-month experience emphasizing the risk of false-negative results., Journal of Clinical Oncology, vol.28, issue.15_suppl, 2010.
DOI : 10.1200/jco.2010.28.15_suppl.3572

J. Selves, D. Grand, R. Guimbaud, K. Gordien, S. Valmary et al., mutations in colorectal cancer., Journal of Clinical Oncology, vol.28, issue.15_suppl, 2010.
DOI : 10.1200/jco.2010.28.15_suppl.3571

P. Quirke, M. Risio, R. Lambert, L. Von-karsa, and M. Vieth, Quality assurance in pathology in colorectal cancer screening and diagnosis-European recommendations. Virchows Arch, 2009.

C. Duby and R. S. , Analyse en composantes principales, 2006.

B. Falissard, Comprendre et utiliser les statistiques dans les sciences de la vie: Masson, 2005.

J. Jolliffe, Principal component analysis, 2002.

P. Cassin, Analyse des données et des panels de données: De Boeck Université, 1999.

J. Pan, H. Chen, Y. Sun, J. Zhang, and X. Luo, Comparative Proteomic Analysis of Non-small-cell Lung Cancer and Normal Controls Using Serum Label-Free Quantitative Shotgun Technology, Lung, vol.120, issue.10, pp.255-61, 2008.
DOI : 10.1002/ijc.22041

Z. Boyd, Q. Wu, O. Brien, C. Spoerke, J. Savage et al., Proteomic analysis of breast cancer molecular subtypes and biomarkers of response to targeted kinase inhibitors using reverse-phase protein microarrays, Molecular Cancer Therapeutics, vol.7, issue.12, pp.3695-706, 2008.
DOI : 10.1158/1535-7163.MCT-08-0810

K. Verhoeckx, S. Bijlsma, E. De-groene, R. Witkamp, J. Van-der-greef et al., A combination of proteomics, principal component analysis and transcriptomics is a powerful tool for the identification of biomarkers for macrophage maturation in the U937 cell line, PROTEOMICS, vol.4, issue.4, pp.1014-1042, 2004.
DOI : 10.1002/pmic.200300669

J. Pagès, Analyse factorielle multiple appliquée aux variables qualitatives et aux données mixtes. Revue de Statistique Appliquée, pp.5-37, 2002.

A. Miyanaga, A. Gemma, R. Noro, K. Kataoka, K. Matsuda et al., Antitumor activity of histone deacetylase inhibitors in non-small cell lung cancer cells: development of a molecular predictive model, Molecular Cancer Therapeutics, vol.7, issue.7, pp.1923-1953, 2008.
DOI : 10.1158/1535-7163.MCT-07-2140

S. Bouali, Transfert des gènes p53 et pten par vectorisation non virale : effet proapoptotique et potentialisation de le réponse cellulaire au cétuximab -Thèse d'université, 2008.

J. Mriouah, Etude de l'impact de la perte d'expression de PTEN sur la réponse cellulaire au cetuximab et l'induction de l'angiogenèse par un modèle cellulaire de carcinome épidermoïde de la tête et du cou, 2010.

I. Pinhel, F. Macneill, M. Hills, J. Salter, S. Detre et al., Extreme loss of immunoreactive p-Akt and p-Erk1/2 during routine fixation of primary breast cancer, Breast Cancer Research, vol.28, issue.Suppl, p.76, 2010.
DOI : 10.1200/JCO.2009.26.1602

S. Siddiqui and D. Rimm, Pre-analytic variables and phospho-specific antibodies: the Achilles heel of immunohistochemistry, Breast Cancer Research, vol.22, issue.6, p.113, 2010.
DOI : 10.1038/modpathol.2009.117

V. Espina, C. Mueller, K. Edmiston, M. Sciro, E. Petricoin et al., Tissue is alive: New technologies are needed to address the problems of protein biomarker pre-analytical variability, PROTEOMICS - CLINICAL APPLICATIONS, vol.121, issue.8, pp.874-82, 2009.
DOI : 10.1016/S0002-9440(10)64472-0

D. Rimm and I. Beyond, Accurate, Reproducible, and Quantitative Measurement of Protein Analyte Concentrations in Fixed Tissue. College of American Pathologists Foundation's Futurescape conference, 2009.

M. Scartozzi, I. Bearzi, R. Berardi, A. Mandolesi, C. Pierantoni et al., Epidermal growth factor receptor (EGFR) downstream signalling pathway in primary colorectal tumours and related metastatic sites: optimising EGFR-targeted treatment options, British Journal of Cancer, vol.1, issue.1, 2007.
DOI : 10.1038/sj.bjc.6603847

M. Ratain and R. Glassman, Biomarkers in phase I oncology trials: signal, noise, or expensive distraction? Clin Cancer Res, Nov, vol.151322, issue.1, pp.6545-6553, 2007.

V. Belief, F. Boissiere, F. Bibeau, C. Desmetz, M. Berthe et al., Proteomic analysis of RCL2 paraffin-embedded tissues, J Cell Mol Med, vol.12, issue.5B, pp.2027-2063, 2008.

C. Delfour, P. Roger, C. Bret, M. Berthe, P. Rochaix et al., RCL2, a New Fixative, Preserves Morphology and Nucleic Acid Integrity in Paraffin-Embedded Breast Carcinoma and Microdissected Breast Tumor Cells, The Journal of Molecular Diagnostics, vol.8, issue.2, pp.157-69, 2006.
DOI : 10.2353/jmoldx.2006.050105

D. Gruson and S. Bodovitz, Rapid emergence of multimarker strategies in laboratory medicine, Biomarkers, vol.55, issue.6, pp.289-96, 2010.
DOI : 10.1002/hep.20506

G. Ruiz, M. Floor, K. Steinberg, S. Grunberg, K. Thunnissen et al., Combined assessment of EGFR pathway-related molecular markers and prognosis of NSCLC patients, British Journal of Cancer, vol.9, issue.1, pp.145-52, 2009.
DOI : 10.1158/1078-0432.CCR-05-1492

A. Sartore-bianchi, D. Nicolantonio, F. Nichelatti, M. Molinari, F. et al., Multi-Determinants Analysis of Molecular Alterations for Predicting Clinical Benefit to EGFR-Targeted Monoclonal Antibodies in Colorectal Cancer, PLoS ONE, vol.92, issue.10, p.7287, 2009.
DOI : 10.1371/journal.pone.0007287.t005

I. Mellinghoff, M. Wang, I. Vivanco, D. Haas-kogan, S. Zhu et al., Molecular Determinants of the Response of Glioblastomas to EGFR Kinase Inhibitors, New England Journal of Medicine, vol.353, issue.19, pp.2012-2036, 2005.
DOI : 10.1056/NEJMoa051918

L. Bonetta, Interactome under construction, Nature, vol.464, issue.7325, 2010.
DOI : 10.1038/468851a

B. Kholodenko, Employing Systems Biology to Quantify Receptor Tyrosine Kinase Signaling in Time and Space Springer, 2010.

B. Kholodenko, J. Hancock, and W. Kolch, Signalling ballet in space and time, Nature Reviews Molecular Cell Biology, vol.3, issue.6, pp.414-440
DOI : 10.1038/msb.2009.19

R. Simon, Clinical trial designs for evaluating the medical utility of prognostic and predictive biomarkers in oncology, Personalized Medicine, vol.6, issue.1, pp.33-47, 2010.
DOI : 10.1002/sim.2825

L. Mcshane, D. Altman, W. Sauerbrei, S. Taube, M. Gion et al., REporting recommendations for tumour MARKer prognostic studies (REMARK), Eur J Cancer, 2005.

A. Vickers, K. Jang, D. Sargent, H. Lilja, and M. Kattan, Systematic review of statistical methods used in molecular marker studies in cancer, Cancer, vol.26, issue.8, pp.1862-1870, 2008.
DOI : 10.1155/2004/202031