This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Scartozzi, M. Articles by Cascinu, S. Search for Related Content PubMed PubMed Citation Articles by Scartozzi, M. Articles by Cascinu, S. Social Bookmarking                            What's this?

Epidermal Growth Factor Receptor (EGFR) Status in Primary Colorectal Tumors Does Not Correlate With EGFR Expression in Related Metastatic Sites: Implications for Treatment With EGFR-Targeted Monoclonal Antibodies

From the Clinica di Oncologia Medica, Istituto di Anatomia Patologica; Azienda Ospedaliera Ospedali Riuniti; Università Politecnica delle Marche, Ancona, Italy

Address reprint requests to Stefano Cascinu, MD, Clinica di Oncologia Medica, Azienda Ospedaliera Ospedali Riuniti-Università Politecnica delle Marche, via Conca, 60,020 Ancona, Italy; e-mail: cascinu{at}yahoo.com

PURPOSE: We hypothesized that the detection of epidermal growth factor receptor (EGFR) expression performed in primary tumors for treatment with EGFR-targeted monoclonal antibodies could not always correlate with EGFR status in metastatic sites, thus making cancer cells in these sites resistant to therapy. The aim of our study was to correlate EGFR expression on primary tumors and related metastases in order to find out whether assessing EGFR status on primary cancer is to be considered an effective tool for planning treatment with EGFR-targeted antibodies.

PATIENTS AND METHODS: We retrospectively evaluated EGFR immunohistochemistry from primary tumors and related metastatic sites in 99 colorectal cancer patients. The site of primary tumor was colon in 77 patients (78%) and rectum in 22 patients (22%). Metastatic sites analyzed were liver in 84 patients (81%), lung in 13 patients (13%), bone in one patient (1%), and brain in five patients (5%). EGFR status was defined as positive if the percentage of malignant cells stained was 1%.

RESULTS: EGFR status was positive in 53 primary tumors (53%). In 19 primary tumors expressing EGFR (36%), the corresponding metastatic site was found negative, whereas it was found positive in seven metastases (15%) from EGFR-negative primary cancers. The difference between these two groups of patients (ie, EGFR-positive to EGFR-negative v EGFR-negative to EGFR-positive) was statistically significant (P = .036).

CONCLUSION: Our results suggest that the detection of the EGFR in primary colorectal cancer could be inadequate for planning therapy with EGFR-targeted monoclonal antibodies in a considerable proportion of both EGFR-positive and -negative primary tumors (36% and 15%, respectively).

Preliminary results of this analysis have been submitted to the European Society of Medical Oncology for presentation at the 2004 meeting.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				F. Loupakis, C. Cremolini, G. Fontanini, I. Stasi, L. Salvatore, and A. Falcone Review: Beyond KRAS: perspectives on new potential markers of intrinsic and acquired resistance to epidermal growth factor receptor inhibitors in metastatic colorectal cancer Therapeutic Advances in Medical Oncology, November 1, 2009; 1(3): 167 - 181. [Abstract] [PDF]

				S. Siena, A. Sartore-Bianchi, F. Di Nicolantonio, J. Balfour, and A. Bardelli Biomarkers Predicting Clinical Outcome of Epidermal Growth Factor Receptor-Targeted Therapy in Metastatic Colorectal Cancer J Natl Cancer Inst, October 7, 2009; 101(19): 1308 - 1324. [Abstract] [Full Text] [PDF]

				F. Loupakis, L. Pollina, I. Stasi, A. Ruzzo, M. Scartozzi, D. Santini, G. Masi, F. Graziano, C. Cremolini, E. Rulli, et al. PTEN Expression and KRAS Mutations on Primary Tumors and Metastases in the Prediction of Benefit From Cetuximab Plus Irinotecan for Patients With Metastatic Colorectal Cancer J. Clin. Oncol., June 1, 2009; 27(16): 2622 - 2629. [Abstract] [Full Text] [PDF]

				J B Arnes, L R Begin, I Stefansson, J-S Brunet, T O Nielsen, W D Foulkes, and L A Akslen Expression of epidermal growth factor receptor in relation to BRCA1 status, basal-like markers and prognosis in breast cancer J. Clin. Pathol., February 1, 2009; 62(2): 139 - 146. [Abstract] [Full Text] [PDF]

				D. Santini, F. Loupakis, B. Vincenzi, I. Floriani, I. Stasi, E. Canestrari, E. Rulli, P. E. Maltese, F. Andreoni, G. Masi, et al. High Concordance of KRAS Status Between Primary Colorectal Tumors and Related Metastatic Sites: Implications for Clinical Practice Oncologist, December 1, 2008; 13(12): 1270 - 1275. [Abstract] [Full Text] [PDF]

				J. Greshock, J. Cheng, D. Rusnak, A. M. Martin, R. Wooster, T. Gilmer, K. Lee, B. L. Weber, and T. Zaks Genome-wide DNA copy number predictors of lapatinib sensitivity in tumor-derived cell lines Mol. Cancer Ther., April 1, 2008; 7(4): 935 - 943. [Abstract] [Full Text] [PDF]

				F. Cappuzzo, G. Finocchiaro, E. Rossi, P.A. Janne, C. Carnaghi, C. Calandri, K. Bencardino, C. Ligorio, F. Ciardiello, T. Pressiani, et al. EGFR FISH assay predicts for response to cetuximab in chemotherapy refractory colorectal cancer patients Ann. Onc., April 1, 2008; 19(4): 717 - 723. [Abstract] [Full Text] [PDF]

				M. Jhawer, S. Goel, A. J. Wilson, C. Montagna, Y.-H. Ling, D.-S. Byun, S. Nasser, D. Arango, J. Shin, L. Klampfer, et al. PIK3CA Mutation/PTEN Expression Status Predicts Response of Colon Cancer Cells to the Epidermal Growth Factor Receptor Inhibitor Cetuximab Cancer Res., March 15, 2008; 68(6): 1953 - 1961. [Abstract] [Full Text] [PDF]

				F. Yang, D. Fu, Q. Ni, F. Fraggetta, G. Pelosi, F. Roila, M. C. Garassino, C. Mantica, E. van der Spek, G. S. Sonke, et al. Cetuximab for Colorectal Cancer N. Engl. J. Med., March 13, 2008; 358(11): 1195 - 1197. [Full Text] [PDF]

				M. Scartozzi, I. Bearzi, C. Pierantoni, A. Mandolesi, F. Loupakis, A. Zaniboni, V. Catalano, A. Quadri, F. Zorzi, R. Berardi, et al. Nuclear Factor-kB Tumor Expression Predicts Response and Survival in Irinotecan-Refractory Metastatic Colorectal Cancer Treated With Cetuximab-Irinotecan Therapy J. Clin. Oncol., September 1, 2007; 25(25): 3930 - 3935. [Abstract] [Full Text] [PDF]

				W. A. Messersmith and M. Hidalgo Panitumumab, a Monoclonal Anti Epidermal Growth Factor Receptor Antibody in Colorectal Cancer: Another One or the One? Clin. Cancer Res., August 15, 2007; 13(16): 4664 - 4666. [Full Text] [PDF]

				J. Kurai, H. Chikumi, K. Hashimoto, K. Yamaguchi, A. Yamasaki, T. Sako, H. Touge, H. Makino, M. Takata, M. Miyata, et al. Antibody-Dependent Cellular Cytotoxicity Mediated by Cetuximab against Lung Cancer Cell Lines Clin. Cancer Res., March 1, 2007; 13(5): 1552 - 1561. [Abstract] [Full Text] [PDF]

				B. Rubio-Viqueira, H. Mezzadra, M. E. Nielsen, A. Jimeno, X. Zhang, C. Iacobuzio-Donahue, A. Maitra, M. Hidalgo, and S. Altiok Optimizing the development of targeted agents in pancreatic cancer: tumor fine-needle aspiration biopsy as a platform for novel prospective ex vivo drug sensitivity assays Mol. Cancer Ther., February 1, 2007; 6(2): 515 - 523. [Abstract] [Full Text] [PDF]

				X. Wang, S. Zhang, G. T. MacLennan, J. N. Eble, A. Lopez-Beltran, X. J. Yang, C.-X. Pan, H. Zhou, R. Montironi, and L. Cheng Epidermal Growth Factor Receptor Protein Expression and Gene Amplification in Small Cell Carcinoma of the Urinary Bladder Clin. Cancer Res., February 1, 2007; 13(3): 953 - 957. [Abstract] [Full Text] [PDF]

				E. Van Cutsem Challenges in the Use of Epidermal Growth Factor Receptor Inhibitors in Colorectal Cancer Oncologist, October 1, 2006; 11(9): 1010 - 1017. [Abstract] [Full Text] [PDF]

				M. Hidalgo, M. L. Amador, A. Jimeno, H. Mezzadra, P. Patel, A. Chan, M. E. Nielsen, A. Maitra, and S. Altiok Assessment of gefitinib- and CI-1040-mediated changes in epidermal growth factor receptor signaling in HuCCT-1 human cholangiocarcinoma by serial fine needle aspiration. Mol. Cancer Ther., July 1, 2006; 5(7): 1895 - 1903. [Abstract] [Full Text] [PDF]

				D. A Frieze and J. S McCune Current Status of Cetuximab for the Treatment of Patients with Solid Tumors Ann. Pharmacother., February 1, 2006; 40(2): 241 - 250. [Abstract] [Full Text] [PDF]

				T. De Pas, C. Putzu, G. Pelosi, G. Curigliano, C. Noberasco, G. Zampino, N. Fazio, V. Formica, L. Spaggiari, and F. de Braud Target-Treatment and Patients' Selection: Can We Still Neglect the Timing of Tissue Collection? J. Clin. Oncol., September 1, 2005; 23(25): 6274 - 6275. [Full Text] [PDF]

				J. P. Spano and G. Milano Reply to the "Letter to the Editor on 'Relevance of EGFR expression in colorectal cancer'" by C. Alliot (Ann Oncol 2005; 16: 1557) Ann. Onc., September 1, 2005; 16(9): 1558 - 1559. [Full Text] [PDF]

				A. Italiano, M.-C. Saint-Paul, F.-X. Caroli-Bosc, E. Francois, A. Bourgeon, D. Benchimol, J. Gugenheim, and J.-F. Michiels Epidermal growth factor receptor (EGFR) status in primary colorectal tumors correlates with EGFR expression in related metastatic sites: biological and clinical implications Ann. Onc., September 1, 2005; 16(9): 1503 - 1507. [Abstract] [Full Text] [PDF]

				M.-P. Bralet, B. Paule, R. Adam, and C. Guettier Loss of Epidermal Growth Factor Receptor Expression in Lymph Node and Liver Metastases of Colon Carcinoma J. Clin. Oncol., August 20, 2005; 23(24): 5844 - 5844. [Full Text] [PDF]

				M. Scartozzi, R. Berardi, I. Bearzi, and S. Cascinu In Reply: J. Clin. Oncol., August 20, 2005; 23(24): 5844 - 5855. [Full Text] [PDF]

				N Andre and W Schmiegel CHEMORADIOTHERAPY FOR COLORECTAL CANCER Gut, August 1, 2005; 54(8): 1194 - 1202. [Full Text] [PDF]