3561 Cetuximab has been shown to be active in the metastatic colorectal cancer, but EGFR detection by immunohistochemistry is not predictive for tumor response. Moroni et al (Lancet Oncology 2005) showed that, in patients responsive to Cetuximab, EGFR gene copy number, assessed by FISH, was increased. On this basis, copy number and protein status of EGFR were investigated in 70 primary and/or metastatic colorectal carcinomas. Protein expression was assessed by immunohistochemistry (IHC) using DAKO EGFRPharmDX kit. Gene and chromosome 7 copy numbers were identified by fluorescent in situ hybridization (FISH). Dual-target, dual-color FISH assays were performed using the LSI EGFR SpectrumOrange/CEP 7 Spectrum Green probe. EGFR gene copy number, chromosome 7 copy number and the average EGFR gene to chromosome 7 signal ratio were reported as FISH genetic variables. Chromosome 7 was polysomic when cancer cells showed multiple centromere signals: low polysomy (2 to 5 signals), high polysomy (>5 signals). Samples with a ratio value ≥ 2.0 were considered to be amplified. EGFR protein was overexpressed in 57 out of 70 patients (81%). In the group of 58 patients evaluated as polysomic, 48 (82,7%) had a low polysomy level, whereas 20 (12.7%) had a high polysomy level. Gene amplification was seen only in 3/70 patients. High polysomy was evidenced only in the group of patients displaying an EGFR IHC score 2+/3+. Forty-six pretreated patients received a cetuximab-based treatment. Response to treatment has been already evaluated in 26 FISH-negative patients while for the other 20 it is still too early. We observed 7 PR (27%), 9 SD (35%) and 10 PD (38%). This study shows that in this series of advanced colorectal cancer patients, EGFR amplification, measured by FISH, is a rare event (4%) and could be considered together with chromosome 7 polysomy for the antitumor activity. No significant financial relationships to disclose.
The role of primary tumour sidedness, EGFR gene copy number and EGFR promoter methylation in RAS/BRAF wild type colorectal cancer patients receiving irinotecan/cetuximab
