4021 Background: In colorectal cancer, biological mechanisms underlying response or resistance to cetuximab, a monoclonal antibody against the extracellular domain of the EGFR are not defined. Small retrospective studies suggested that EGFR increased gene copy number measured by fluorescence in situ hybridization (FISH) or presence of KRAS mutations were associated with cetuximab response or resistance, respectively. This study aimed to identify biological predictors for sensitivity/resistance to cetuximab treatment in colorectal cancer. We also compared biomarker results in primary tumors and corresponding metastases. Methods: We analyzed EGFR (IHC, FISH), HER2 (FISH), and KRAS (mutation) in paraffin embedded tumor blocks from 85 colorectal cancer patients treated with cetuximab. For FISH analyses, a positive result was defined according to criteria described in breast (Wolff et al. J Clin Oncol 2007), lung (Cappuzzo et al. JNCI 2005) and colorectal cancer (Moroni et al. Lancet Oncology 2005). EGFR, HER2...