EGFR FISH assay predicts for response to cetuximab in chemotherapy refractory colorectal cancer patients

Cappuzzo, F.; Finocchiaro, G.; Rossi, E.; Jänne, P.A.; Carnaghi, C.; Calandri, C.; Bencardino, K.; Ligorio, C.; Ciardiello, F.; Pressiani, T.; Destro, A.; Roncalli, M.; Crino, L.; Franklin, W.A.; Santoro, A.; Varella-Garcia, M.

doi:10.1093/annonc/mdm492

Cited by 267Colorectal Cancer Treatments and StudiesHER2/EGFR in Cancer ResearchLung Cancer Treatments and Mutations

EGFR FISH assay predicts for response to cetuximab in chemotherapy refractory colorectal cancer patients

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Cappuzzo, F., Finocchiaro, G., Rossi, E., Jänne, P.A., Carnaghi, C., Calandri, C., Bencardino, K., Ligorio, C. +8 more·2008·Annals of Oncology

DOI 10.1093/annonc/mdm492

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Abstract

Background Standardized conditions to distinguish subpopulations of colorectal cancer (CRC) patients more and less sensitive to cetuximab therapy remain undefined.Materials and methods We retrospectively analyzed epidermal growth factor receptor (EGFR) copy number by fluorescence in situ hybridization (FISH) in paraffin-embedded tumor blocks from 85 chemorefractory CRC patients treated with cetuximab. Results were analyzed according to different score systems previously reported in colorectal and lung cancers. The primary end point of the study was identification of the EGFR FISH score that best associates with response rate (RR).Results Using receiver operating characteristic (ROC) analysis, the cut-off that best discriminated responders versus nonresponders to cetuximab was a mean of 2.92 EGFR gene copies per cell. This model showed sensitivity of 58.6% [95% confidence interval (CI) = 47.1-70.1) and specificity of 93.3% (95% CI = 80.6-100). EGFR FISH-positive patients (N = 43, 50.6%) had significantly higher RR (P = 0.0001) and significantly longer time to disease progression (P = 0.02) than EGFR FISH negative (N = 42, 49.4%). Other scoring systems resulted less accurate in discriminating patients with the highest likelihood of response to cetuximab therapy.Conclusions CRC patients with high EGFR gene copy number have an increased likelihood to respond to cetuximab therapy. Prospective clinical trials with a careful standardization of assay conditions and pattern interpretation are urgently needed.

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Increased EGFR gene copy number could predict response among KRAS wild-type patients.
“Increased EGFR gene copy number could predict response among KRAS wild-type patients [53, 91, 111-113]”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [113]

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Mohan, S., Heitzer, E., Ulz, P., Lafer, I., Lax, S., Auer, M., Pichler, M., Gerger, A., Eisner, F., Höefler, G., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004271 · Cited by 175 · see citing works
Epidermal growth factor receptor inhibitors in cancer treatment: advances, challenges and opportunities
Modjtahedi, H., & Essapen, S. (2009) · Anti-Cancer Drugs · doi:10.1097/cad.0b013e3283330590 · Cited by 175 · see citing works
Clinical Usefulness of EGFR Gene Copy Number as a Predictive Marker in Colorectal Cancer Patients Treated with Cetuximab: A Fluorescent In situ Hybridization Study
Personeni, N., Fieuws, S., Piessevaux, H. H., Hertogh, G. D., Schutter, J. D., Biesmans, B., Roock, W. D., Capoen, A., Dêbiec‐Rychter, M., Laethem, J. V., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0449 · Cited by 173 · see citing works
Predictive value of epidermal growth factor receptor expression for first-line chemotherapy plus cetuximab in patients with head and neck and colorectal cancer: Analysis of data from the EXTREME and CRYSTAL studies
Licitra, L. F., Störkel, S., Kerr, K. M., Cutsem, E. V., Pirker, R., Hirsch, F. R., Vermorken, J. B., von Heydebreck, A., Esser, R., Celik, I., et al. (2012) · European Journal of Cancer · doi:10.1016/j.ejca.2012.11.018 · Cited by 167 · see citing works
Self-citation
A Review of the Most Promising Biomarkers in Colorectal Cancer: One Step Closer to Targeted Therapy
Deschoolmeester, V., Baay, M. F. D., Specenier, P. M., Lardon, F., & Vermorken, J. B. (2010) · The Oncologist · doi:10.1634/theoncologist.2010-0025 · Cited by 168 · see citing works
HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients
Martin, V, Landi, L., Molinari, F., Fountzilas, G., Geva, R., Riva, A., Saletti, P., De Dosso, S., Spitale, A., Tejpar, S., et al. (2013) · British Journal of Cancer · doi:10.1038/bjc.2013.4 · Cited by 156 · see citing works
Self-citation
Increased Detection Sensitivity for KRAS Mutations Enhances the Prediction of Anti-EGFR Monoclonal Antibody Resistance in Metastatic Colorectal Cancer
Molinari, F., Felicioni, L., Buscarino, M., De Dosso, S., Buttitta, F., Malatesta, S., Movilia, A., Luoni, M., Boldorini, R., Alabiso, O., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-3137 · Cited by 159 · see citing works
Detection of KRAS and BRAF Mutations in Colorectal Carcinoma
Arcila, M. E., Lau, C., Nafa, K., & Ladanyi, M. (2011) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2010.11.005 · Cited by 137 · see citing works
Phase II study and biomarker analysis of cetuximab combined with modified FOLFOX6 in advanced gastric cancer
Han, S.-W., Oh, D.-Y., Im, S., Park, S. R., Lee, K.-W., SONG, H. S., Lee, N. S., Lee, K. H., Choi, I. S., Lee, M. H., et al. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6604861 · Cited by 136 · see citing works
Dasatinib sensitizes KRAS mutant colorectal tumors to cetuximab
Dunn, E. F., Iida, M., Myers, R. A., Campbell, D. A., Hintz, K. A., Armstrong, E. A., Li, C., & Wheeler, D. L. (2011) · Oncogene · doi:10.1038/onc.2010.430 · Cited by 133 · see citing works
“Furthermore, it has been demonstrated in several clinical trials that patients with mCRC and a KRAS mutation do not respond to cetuximab therapy (Lievre et al., 2006; Benvenuti et al., 2007; Di Fiore et al., 2007; Khambata-Ford et al., 2007; Cappuzzo et al., 2008; De Roock et al., 2008; Karapetis et al., 2008).”
Background
Mutations and Response to Epidermal Growth Factor Receptor Inhibitors
Laurent‐Puig, P., Lièvre, A., & Blons, H. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0905 · Cited by 133 · see citing works
Differing deregulation of EGFR and downstream proteins in primary colorectal cancer and related metastatic sites may be clinically relevant
Molinari, F., Martin, V, Saletti, P., De Dosso, S., Spitale, A., Camponovo, A., Bordoni, A., Crippa, S., Mazzucchelli, L., & Frattini, M. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6604848 · Cited by 122 · see citing works
Autocrine Production of Amphiregulin Predicts Sensitivity to Both Gefitinib and Cetuximab in EGFR Wild-type Cancers
Yonesaka, K., Zejnullahu, K., Lindeman, N. I., Homes, A. J., Jackman, D. M., Zhao, F., Rogers, A. M., Johnson, B. E., & Janne, P. A. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0957 · Cited by 120 · see citing works
IGF2 is an actionable target that identifies a distinct subpopulation of colorectal cancer patients with marginal response to anti-EGFR therapies
Zanella, E. R., Galimi, F., Sassi, F., Migliardi, G., Cottino, F., Leto, S. M., Lupo, B., Erriquez, J., Isella, C., Comoglio, P. M., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.3010445 · Cited by 117 · see citing works
The role of epidermal growth factor receptor in chordoma pathogenesis: a potential therapeutic target
Shalaby, A. A., Presneau, N., Ye, H., Halai, D., Berisha, F., Idowu, B. D., Leithner, A., Liegl, B., Briggs, T. W. R., Bácsi, K., et al. (2010) · The Journal of Pathology · doi:10.1002/path.2818 · Cited by 118 · see citing works
New Strategies in Head and Neck Cancer: Understanding Resistance to Epidermal Growth Factor Receptor Inhibitors
Chen, L. F., Cohen, E. E. W., & Grandis, J. R. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-2318 · Cited by 117 · see citing works
Promoting antibody-dependent cellular phagocytosis for effective macrophage-based cancer immunotherapy
Cao, X., Chen, J., Li, B., Dang, J., Zhang, W., Zhong, X., Wang, C., Raoof, M., Sun, Z., Yu, J., et al. (2022) · Science Advances · doi:10.1126/sciadv.abl9171 · Cited by 117 · see citing works
KRAS and BRAF mutational status in primary colorectal tumors and related metastatic sites: Biological and clinical implications
Italiano, A., Hostein, I., Soubeyran, I., Fabas, T., Benchimol, D., Evrard, S., Gugenheim, J., Becouarn, Y., Brunet, R., Fonck, M., et al. (2010) · Annals of Surgical Oncology · doi:10.1245/s10434-009-0864-z · Cited by 114 · see citing works
Oncogenic mutations as predictive factors in colorectal cancer
Lièvre, A., Blons, H., & Laurent-Puig, P. (2010) · Oncogene · doi:10.1038/onc.2010.89 · Cited by 117 · see citing works
Treatment in advanced colorectal cancer: what, when and how?
Chau, I., & Cunningham, D. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6605061 · Cited by 112 · see citing works
Pharmacogenomic and Pharmacoproteomic Studies of Cetuximab in Metastatic Colorectal Cancer: Biomarker Analysis of a Phase I Dose-Escalation Study
Tabernero, J., Cervantes, A., Rivera, F., Martinelli, E., Rojo, F., von Heydebreck, A., Macarulla, T., Rodriguez-Braun, E., Eugenia Vega-Villegas, M., Senger, S., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.22.6043 · Cited by 110 · see citing works
Self-citation
EGFR/HER2 in breast cancer: a biological approach for molecular diagnosis and therapy
Milanezi, F., Carvalho, S., & Schmitt, F. C. (2008) · Expert Review of Molecular Diagnostics · doi:10.1586/14737159.8.4.417 · Cited by 109 · see citing works
Tumour gene expression predicts response to cetuximab in patients with KRAS wild-type metastatic colorectal cancer
Baker, J. B., Dutta, D., Watson, D., Maddala, T., Munneke, B., Shak, S., Rowinsky, E. K., Xu, L.-A., Harbison, C. T., Clark, E. A., et al. (2011) · British Journal of Cancer · doi:10.1038/sj.bjc.6606054 · Cited by 107 · see citing works
EGFR-targeted therapy
Vecchione, L., Jacobs, B., Normanno, N., Ciardiello, F., & Tejpar, S. (2011) · Experimental Cell Research · doi:10.1016/j.yexcr.2011.08.021 · Cited by 107 · see citing works
Self-citation
Prognostic and predictive biomarkers for epidermal growth factor receptor-targeted therapy in colorectal cancer: Beyond KRAS mutations
Custodio, A., & Feliú, J. (2012) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2012.05.001 · Cited by 96 · see citing works
Panitumumab combined with irinotecan for patients with KRAS wild-type metastatic colorectal cancer refractory to standard chemotherapy: a GERCOR efficacy, tolerance, and translational molecular study
André, T., Blons, H., Mabro, M., Chibaudel, B., Bachet, J., Tournigand, C., Bennamoun, M., Artru, P., Nguyen, S., Ebenezer, C., et al. (2012) · Annals of Oncology · doi:10.1093/annonc/mds465 · Cited by 93 · see citing works
Correlation of dynamic contrast‐enhanced MRI perfusion parameters with angiogenesis and biologic aggressiveness of rectal cancer: Preliminary results
Yeo, D. M., Oh, S. N., Jung, C., Lee, M. A., Oh, S. T., Rha, S. E., Jung, S. E., Byun, J. Y., Gall, P., & Son, Y. (2013) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.24541 · Cited by 90 · see citing works
Epidermal growth factor receptor gene copy number, K-ras mutation and pathological response to preoperative cetuximab, 5-FU and radiation therapy in locally advanced rectal cancer
Bengala, C., Bettelli, S. R., Bertolini, F., Salvi, S., Chiara, S., Sonaglio, C., Losi, L., Bigiani, N., Sartori, G., Dealis, C., et al. (2008) · Annals of Oncology · doi:10.1093/annonc/mdn647 · Cited by 89 · see citing works
Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies
Leto, S. M., & Trusolino, L. (2014) · Journal of Molecular Medicine · doi:10.1007/s00109-014-1161-2 · Cited by 87 · see citing works
TP53 mutations predict disease control in metastatic colorectal cancer treated with cetuximab-based chemotherapy
oden-Gangloff, A., Fiore, F. D., Bibeau, F., Lamy, A., Bougeard, G., Charbonnier, F., Blanchard, F., Tougeron, D., Ychou, M., Boissière‐Michot, F., et al. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6605008 · Cited by 84 · see citing works
Heterogeneity of KRAS status may explain the subset of discordant KRAS status between primary and metastatic colorectal cancer
Watanabe, T., Kobunai, T., Yamamoto, Y., Matsuda, K., Ishihara, S., Nozawa, K., Iinuma, H., Shibuya, H., & Eshima, K. (2011) · Diseases of the Colon & Rectum · doi:10.1097/dcr.0b013e31821d37a3 · Cited by 82 · see citing works
TTF1 expression in non‐small cell lung carcinoma: association with TTF1 gene amplification and improved survival
Perner, S., Wagner, P., Soltermann, A., Lafargue, C. J., Tischler, V., Weir, B. A., Weder, W., Meyerson, M. M., Giordano, T. J., Moch, H., et al. (2008) · The Journal of Pathology · doi:10.1002/path.2443 · Cited by 81 · see citing works
Prognostic value of cetuximab‐related skin toxicity in metastatic colorectal cancer patients and its correlation with parameters of the epidermal growth factor receptor signal transduction pathway: Results from a randomized trial of the GERMAN AIO CRC Study Group
Stintzing, S., Kapaun, C., Laubender, R. P., Jung, A., Neumann, J. H. L., Modest, D. P., Giessen, C. A., Moosmann, N., Wollenberg, A., Kirchner, T., et al. (2012) · International Journal of Cancer · doi:10.1002/ijc.27654 · Cited by 81 · see citing works
Efficacy of the Monoclonal Antibody EGFR Inhibitors for the Treatment of Metastatic Colorectal Cancer
Fakih, M., & Wong, R. (2010) · Current Oncology · doi:10.3747/co.v17is1.616 · Cited by 76 · see citing works
Molecular Markers in the Treatment of Metastatic Colorectal Cancer
Wilson, P. M., LaBonte, M. J., & Lenz, H. (2010) · The Cancer Journal · doi:10.1097/ppo.0b013e3181e07738 · Cited by 76 · see citing works
The importance of KRAS mutations and EGF61A>G polymorphism to the effect of cetuximab and irinotecan in metastatic colorectal cancer
Spindler, K.-L. G., Pallisgaard, N., Rasmussen, A. A., Lindebjerg, J., Andersen, R. F., Crüger, D. G., & Jakobsen, A. K. M. (2009) · Annals of Oncology · doi:10.1093/annonc/mdn712 · Cited by 75 · see citing works
Colorectal Cancer Subtypes: Developmental Origin and Microenvironmental Regulation
Fessler, E., & Medema, J. P. (2016) · Trends in cancer · doi:10.1016/j.trecan.2016.07.008 · Cited by 74 · see citing works
Epidermal Growth Factor Receptor (EGFR) gene copy number (GCN) correlates with clinical activity of irinotecan-cetuximab in K-RAS wild-type colorectal cancer: a fluorescence in situ (FISH) and chromogenic in situ hybridization (CISH) analysis
Scartozzi, M., Bearzi, I., Mandolesi, A., Pierantoni, C., Loupakis, F., Zaniboni, A., Negri, F., Quadri, A., Zorzi, F., Galizia, E., et al. (2009) · BMC Cancer · doi:10.1186/1471-2407-9-303 · Cited by 72 · see citing works
Molecular determinants of anti-EGFR sensitivity and resistance in metastatic colorectal cancer
Fiore, F. D., Sesboüé, R., Michel, P., Sabourin, J., & Frébourg, T. (2010) · British Journal of Cancer · doi:10.1038/sj.bjc.6606008 · Cited by 71 · see citing works
Patient-derived xenograft (PDX) models of colorectal carcinoma (CRC) as a platform for chemosensitivity and biomarker analysis in personalized medicine
Rivera, M., Fichtner, I., Wulf-Goldenberg, A., Sers, C., Merk, J., Patone, G., Merve, K., Kanashova, T., Mertins, P., Hoffmann, J., et al. (2020) · Neoplasia · doi:10.1016/j.neo.2020.11.005 · Cited by 71 · see citing works
Analysis of KRAS, BRAF, PTEN, IGF1R, EGFR intron 1 CA status in both primary tumors and paired metastases in determining benefit from cetuximab therapy in colon cancer
Park, J. H., Han, S., Oh, D., Im, S., Jeong, S., Park, K. J., Kim, T., Bang, Y., & Park, J.-G. (2011) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-011-1586-z · Cited by 70 · see citing works
Role of targeted agents in metastatic colorectal cancer
Prenen, H., Vecchione, L., & Cutsem, E. V. (2013) · Targeted Oncology · doi:10.1007/s11523-013-0281-x · Cited by 69 · see citing works
Predictive and Prognostic Markers in Colorectal Cancer
George, B., & Kopetz, S. (2011) · Current Oncology Reports · doi:10.1007/s11912-011-0162-3 · Cited by 65 · see citing works
EGFR Gene Copy Number as a Prognostic Marker in Colorectal Cancer Patients Treated with Cetuximab or Panitumumab: A Systematic Review and Meta Analysis
Jiang, Z., Li, C., Li, F., & Wang, X. (2013) · PLoS ONE · doi:10.1371/journal.pone.0056205 · Cited by 64 · see citing works
Linking somatic genetic alterations in cancer to therapeutics
Stuart, D. D., & Sellers, W. R. (2009) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.02.001 · Cited by 65 · see citing works
Molecular markers for novel therapies in neuroendocrine (carcinoid) tumors
Gilbert, J. A., Adhikari, L., Lloyd, R. V., Rubin, J., Haluska, P., Carboni, J. M., Gottardis, M. M., & Ames, M. M. (2010) · Endocrine Related Cancer · doi:10.1677/erc-09-0318 · Cited by 63 · see citing works
Improving Response Rates to EGFR-Targeted Therapies for Head and Neck Squamous Cell Carcinoma: Candidate Predictive Biomarkers and Combination Treatment with Src Inhibitors
Egloff, A. M., & Grandis, J. R. (2009) · Journal of Oncology · doi:10.1155/2009/896407 · Cited by 62 · see citing works
Clinico-pathological and biological prognostic variables in squamous cell carcinoma of the vulva
Gadducci, A., Tana, R., Barsotti, C., Guerrieri, M. E., & Genazzani, A. R. (2011) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2011.09.003 · Cited by 62 · see citing works
Targeted therapy of cancer: new roles for pathologists in colorectal cancer
Hamilton, S. R. (2008) · Modern Pathology · doi:10.1038/modpathol.2008.14 · Cited by 62 · see citing works
Cetuximab in the treatment of patients with colorectal cancer
Garrett, C. R., & Eng, C. (2011) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2011.582464 · Cited by 60 · see citing works
Imaging EGFR and HER2 by PET and SPECT: A Review
Corcoran, E. B., & Hanson, R. N. (2013) · Medicinal Research Reviews · doi:10.1002/med.21299 · Cited by 61 · see citing works
Revisiting Epidermal Growth Factor Receptor (EGFR) Amplification as a Target for Anti-EGFR Therapy: Analysis of Cell-Free Circulating Tumor DNA in Patients With Advanced Malignancies
Kato, S., Okamura, R., Mareboina, M., Lee, S., Goodman, A. M., Patel, S. P., Fanta, P. T., Schwab, R. B., Vu, P., Raymond, V. M., et al. (2019) · JCO Precision Oncology · doi:10.1200/po.18.00180 · Cited by 61 · see citing works
Markers of resistance to anti-EGFR therapy in colorectal cancer.
Shaib, W. L., Mahajan, R., & El‐Rayes, B. F. (2013) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2078-6891.2013.029 · Cited by 58 · see citing works
Decreased survival in EGFR gene amplified vulvar carcinoma
Growdon, W. B., Boisvert, S. L., Akhavanfard, S., Oliva, E., Dias-Santagata, D. C., Kojiro, S., Horowitz, N. S., Iafrate, A. J., Borger, D. R., & Rueda, B. R. (2008) · Gynecologic Oncology · doi:10.1016/j.ygyno.2008.07.038 · Cited by 58 · see citing works
EGFR targeted therapies and radiation: Optimizing efficacy by appropriate drug scheduling and patient selection
Cuneo, K. C., Nyati, M. K., Ray, D., & Lawrence, T. S. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2015.07.002 · Cited by 55 · see citing works
Tumor budding predicts response to anti-EGFR therapies in metastatic colorectal cancer patients
Zlobec, I. (2010) · World Journal of Gastroenterology · doi:10.3748/wjg.v16.i38.4823 · Cited by 52 · see citing works
MicroRNA Signature in Metastatic Colorectal Cancer Patients Treated With Anti-EGFR Monoclonal Antibodies
Cappuzzo, F., Sacconi, A., Landi, L. M., Ludovini, V., Biagioni, F., D’Incecco, A., Capodanno, A., Salvini, J., Corgna, E., Cupini, S., et al. (2013) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2013.11.006 · Cited by 53 · see citing works
Self-citation
In vitro and in vivo sensitization of SW620 metastatic colon cancer cells to CDDP-induced apoptosis by the nitric oxide donor DETANONOate: Involvement of AIF
Huerta, S., Baay-Guzman, G. J., González-Bonilla, C. R., Livingston, E. H., Huerta‐Yépez, S., & Bonavida, B. (2008) · Nitric Oxide · doi:10.1016/j.niox.2008.11.006 · Cited by 52 · see citing works
Cetuximab and circadian chronomodulated chemotherapy as salvage treatment for metastatic colorectal cancer (mCRC): safety, efficacy and improved secondary surgical resectability
Lévi, F., Karaboué, A., Gorden, L. D., Innominato, P. F., Saffroy, R., Giacchetti, S., Hauteville, D., Guettier, C., Adam, R. A., & Bouchahda, M. (2010) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-010-1327-8 · Cited by 50 · see citing works
Epidermal growth factor receptor expression and gene copy number in sinonasal intestinal type adenocarcinoma
Franchi, A., Fondi, C., Paglierani, M., Pepi, M., Gallo, O., & Santucci, M. (2009) · Oral Oncology · doi:10.1016/j.oraloncology.2008.12.005 · Cited by 50 · see citing works
Prognostic role of EGFR gene copy number and KRAS mutation in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy
Bengala, C., Bettelli, S. R., Bertolini, F., Sartori, G., Fontana, A., Malavasi, N., Depenni, R., Zironi, S., Giovane, C. D., Luppi, G., et al. (2010) · British Journal of Cancer · doi:10.1038/sj.bjc.6605853 · Cited by 49 · see citing works
Additional value of EGFR downstream signaling phosphoprotein expression to KRAS status for response to anti‐EGFR antibodies in colorectal cancer
Perkins, G., Lièvre, A., Ramacci, C., Méatchi, T., de Reyniès, A., Emile, J., Boige, V., Tomasic, G., Bachet, J., Bibeau, F., et al. (2010) · International Journal of Cancer · doi:10.1002/ijc.25152 · Cited by 48 · see citing works
EGFR amplification and expression in oral squamous cell carcinoma in young adults
COSTA, V. B. B. D., Kowalski, L. P., Coutinho‐Camillo, C. M., Begnami, M. D., Calsavara, V. F., Neves, J. I., & Kaminagakura, E. (2018) · International Journal of Oral and Maxillofacial Surgery · doi:10.1016/j.ijom.2018.01.002 · Cited by 49 · see citing works
Predictive and prognostic biomarkers with therapeutic targets in advanced colorectal cancer
Luo, H. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i14.3858 · Cited by 50 · see citing works
EGFR gene copy number assessment from areas with highest EGFR expression predicts response to anti-EGFR therapy in colorectal cancer
Ålgars, A., Lintunen, M., Carpén, O., Ristamäki, R., & Sundström, J. T. T. (2011) · British Journal of Cancer · doi:10.1038/bjc.2011.223 · Cited by 49 · see citing works
Relationship between epidermal growth factor receptor gene copy number and protein expression in oral cavity squamous cell carcinoma
Huang, S., Cheng, S., Chien, H., Liao, C., Chen, I., Wang, H., Chuang, W., Wang, C., & Hsieh, L. (2011) · Oral Oncology · doi:10.1016/j.oraloncology.2011.06.511 · Cited by 47 · see citing works
Clinical, laboratory and molecular factors predicting chemotherapy efficacy and toxicity in colorectal cancer
Chua, W. M., Kho, P. S., Moore, M. M., Charles, K. A., & Clarke, S. J. (2010) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2010.07.012 · Cited by 45 · see citing works
Analysis of HER-3, insulin growth factor-1, nuclear factor-kB and epidermal growth factor receptor gene copy number in the prediction of clinical outcome for K-RAS wild-type colorectal cancer patients receiving irinotecan-cetuximab.
Scartozzi, M., Giampieri, R., Maccaroni, E., Mandolesi, A., Giustini, L., Silva, R., Zaniboni, A., Biscotti, T., Biagetti, S., Galizia, E., et al. (2012) · Annals of Oncology · doi:10.1093/annonc/mdr558 · Cited by 43 · see citing works
An overview of the epidermal growth factor receptor fluorescence in situ hybridisation challenge in tumour pathology
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The human epidermal growth factor receptor (EGFR) gene in European patients with advanced colorectal cancer harbors infrequent mutations in its tyrosine kinase domain
Metzger, B., Chambeau, L., Begon, D. Y., Faber, C., Kayser, J., Berchem, G., Pauly, M., Boniver, J., Delvenne, P., Dicato, M. A., et al. (2011) · BMC Medical Genetics · doi:10.1186/1471-2350-12-144 · Cited by 46 · see citing works
Experimental results and related clinical implications of PET detection of epidermal growth factor receptor (EGFr) in cancer
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High concordance of BRAF status between primary colorectal tumours and related metastatic sites: implications for clinical practice
Santini, D., Spoto, C., Loupakis, F., Vincenzi, B., Silvestris, N., Cremolini, C., Canestrari, E., Graziano, F., Galluccio, N., Salvatore, L., et al. (2010) · Annals of Oncology · doi:10.1093/annonc/mdq318 · Cited by 46 · see citing works
Biomarker in Colorectal Cancer
Schirripa, M., & Lenz, H. (2016) · The Cancer Journal · doi:10.1097/ppo.0000000000000190 · Cited by 46 · see citing works
Molecular Markers for Novel Therapeutic Strategies in Pancreatic Endocrine Tumors
Gilbert, J. A., Adhikari, L., Lloyd, R. V., Halfdanarson, T. R., Muders, M. H., & Ames, M. M. (2012) · Pancreas · doi:10.1097/mpa.0b013e31826cb243 · Cited by 44 · see citing works

Cetuximab Shows Activity in Colorectal Cancer Patients With Tumors for Which FISH Analysis Does Not Detect an Increase in EGFR Gene Copy Number
Italiano, A., Follana, P., Caroli‐Bosc, F., Badetti, J.-L., Benchimol, D., Garnier, G., Gugenheim, J., Haudebourg, J., Keslair, F., Lesbats, G., et al. (2007) · Annals of Surgical Oncology · doi:10.1245/s10434-007-9667-2 · Cited by 86 · see citing works
Clinical Usefulness of EGFR Gene Copy Number as a Predictive Marker in Colorectal Cancer Patients Treated with Cetuximab: A Fluorescent In situ Hybridization Study
Personeni, N., Fieuws, S., Piessevaux, H. H., Hertogh, G. D., Schutter, J. D., Biesmans, B., Roock, W. D., Capoen, A., Dêbiec‐Rychter, M., Laethem, J. V., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0449 · Cited by 173 · see citing works
Outcome prediction to cetuximab in advanced colorectal cancer: Analysis of EGFR and HER2 gene copy number by fluorescence in situ hybridization
Personeni, N., Hertogh, G. D., Störkel, S., Dêbiec‐Rychter, M., Geboes, K. J., Roock, W. D., Humblet, Y., Piessevaux, H. H., Cutsem, E. V., & Tejpar, S. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.25.18_suppl.10569 · Cited by 1 · see citing works
Annals of Oncology
Finocchiaro, G., Rossi, E., Janne, P. A., Carnaghi, C., Cal, C., Bencardino, K., Ligorio, C., Ciardiello, F., Pressiani, T., Destro, A., et al. (2016)
Self-citation
Epidermal growth factor receptor gene copy number in 101 advanced colorectal cancer patients treated with chemotherapy plus cetuximab
Campanella, C., Mottolese, M., Cianciulli, A. M., Torsello, A., Merola, R., Sperduti, I., Melucci, E., Conti, S., Diodoro, M. G., Zeuli, M., et al. (2010) · Journal of Translational Medicine · doi:10.1186/1479-5876-8-36 · Cited by 20 · see citing works

Authors: Cappuzzo, F., Finocchiaro, G., Rossi, E., Jänne, P. A., Carnaghi, C., Calandri, C., Bencardino, K., Ligorio, C., Ciardiello, F., Pressiani, T., Destro, A., Roncalli, M., Crino, L., Franklin, W. A., Santoro, A., & Varella-Garcia, M.
Affiliations: IRCCS Humanitas Research Hospital (IT)
University of Colorado Cancer Center (US)
Ospedale Bellaria (IT)
Policlinico San Matteo Fondazione (IT)
University of Campania "Luigi Vanvitelli" (IT)
Corresponding author: Cappuzzo, F.
ORCID: Cappuzzo, F.
Finocchiaro, G.
Rossi, E.
Carnaghi, C.
Bencardino, K.
Ciardiello, F.
Pressiani, T.
Destro, A.
Roncalli, M.
Santoro, A.
Venue: Annals of Oncology
Publisher: Elsevier BV
Published: 2008-04
Volume: 19
Issue: 4
Pages: 717-723
ISSN: 0923-7534 (ISSN-L)
DOI: 10.1093/annonc/mdm492
OpenAlex: W2158475201
Cited by: 267
References: 39
Citations by year: 2026: 2 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 6 · 2016: 8 · 2015: 12 · 2014: 18 · 2013: 20 · 2012: 24
FWCI: 18.73
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 4265 d)
Locations: Annals of Oncology (publishedVersion)
PubMed (publishedVersion)
HighWire Press Open Archive (submittedVersion)
Funders: Università degli Studi di Napoli Federico II
Cancer Center, University of Colorado
Topics: Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Keywords: EGFR copy number, cetuximab, colorectal cancer, chemorefractory cancer, predictive biomarkers, treatment response prediction, time to progression, EGFR amplification
MeSH terms: Cetuximab, Adult, Aged, Antibodies, Monoclonal, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Female, Humans, Immunohistochemistry, Italy, Male, Middle Aged, Predictive Value of Tests, Retrospective Studies, ROC Curve, Sensitivity and Specificity, Biomarkers, Tumor, Colorectal Neoplasms, Confidence Intervals, Survival Analysis, Treatment Outcome, In Situ Hybridization, Fluorescence, Disease-Free Survival, Patient Selection, Drug Resistance, Neoplasm, Antibodies, Monoclonal, Humanized, ErbB Receptors

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EGFR FISH assay predicts for response to cetuximab in chemotherapy refractory colorectal cancer patients

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