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10.1245/s10434-007-9667-2
Annals of Surgical Oncology 15:649-654 (2008)
© 2008 Society of Surgical Oncology
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Original Article

Cetuximab Shows Activity in Colorectal Cancer Patients With Tumors for Which FISH Analysis Does Not Detect an Increase in EGFR Gene Copy Number

Antoine Italiano, MD1,2, Philippe Follana, MD1, François-Xavier Caroli, MD3, Jean-Luc Badetti, MD4, Daniel Benchimol, MD3, Georges Garnier, MD5, Jean Gugenheim, MD3, Juliette Haudebourg, MD6, Frédérique Keslair, MS2, Gérard Lesbats, MD7, Gérard Lledo, MD8, Jean-Francois Roussel, MD9, Florence Pedeutour, PharmD, PhD2 and Eric François, MD1

1 Department of Medical Oncology, Centre Antoine-Lacassagne, Canceropôle PACA, Nice, France
2 Laboratory of Solid Tumors Genetics, Centre Hospitalier Universitaire de Nice and CNRS UMR 6543, Facultéde Médecine, Canceropôle PACA, Nice, France
3 Medical Surgical Department of Gastrointestinal Oncology and Hepatology, Centre Hospitalier Universitaire de Nice, Nice, France
4 Department of Gastroenterology, Centre Hospitalier Général de Cannes, Cannes, France
5 Department of Medical Oncology, Centre Hospitalier Princesse Grace, Monaco, Monaco
6 Department of Pathology, Centre Hospitalier Universitaire de Nice, Nice, France
7 Department of Medical Oncology, Clinique Belvedere, Nice, France
8 Department of Medical Oncology, Clinique Saint-Jean, Lyon, France
9 Department of Pathology, Centre Hospitalier Princesse Grace, Monaco, Monaco

Correspondence: Address correspondence and reprint requests to: Antoine Italiano, MD; E-mail: antoine.italiano{at}unice.fr

Background: EGFR (epidermal growth factor receptor) gene gain assessed by FISH (fluorescence in situ hybridization) has been shown to be predictive of response to EGFR-targeted therapies in patients with non–small cell lung cancer. The aim or our study was to relate the EGFR gene copy number to therapeutic results in patients with metastatic colorectal cancer (CRC) treated with a cetuximab-containing regimen.

Methods: Forty-seven patients with metastatic CRC treated with a cetuximab-containing regimen between August 2004 and September 2006 were included in our study. EGFR status was assessed by immunohistochemistry (IHC) and by FISH on fixed paraffin-embedded sections of tumor specimens.

Results: By IHC (n = 47), 39 patients (83%) had EGFR-positive tumors. EGFR gene copy gain was detected in 8 (19.5%) of 41 tumors. Neither EGFR expression assessed by IHC nor EGFR gene copy gain assessed by FISH were statistically significantly correlated with objective response rate, disease control rate, progression-free survival, and overall survival. Of the 33 patients whose tumors were FISH negative, 8 patients (24.2%) had a partial response, and 10 (30.3%) had stable disease.

Conclusions: EGFR FISH analysis does not seem to be a sufficiently robust test for selecting candidate CRC patients for cetuximab therapy.







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