Abstract only 21070 Background: In current clinical practice Cetuximab represents a standard therapy for Irinotecan resistant pts with ACC, where EGFR-immunohistochemistry (IHC) evaluation is positive. In absence of reliable molecular predictors of the clinical benefit to anti-EGFR therapy, we have studied EGFR protein expression and gene status in order to correlate them to the clinical response. Methods: We investigated 40 primary colorectal carcinoma specimens. EGFR-protein expression was evaluated by Immunohistochemistry (IHC) using PharmDX-Kit DAKO Cytomation. IHC evaluation was performed using combined score based on the sum of percentage of positive cells and the staining of each sample. We identified three EGFR-score categories: 0–2, 3–5, 6–7 corresponding to low, intermediate and high expression respectively. EGFR-genetic status was conducted by Dual-Colour FISH (LSI EGFR-probe Vysis Inc).Gene and chromosome 7 copy numbers were identified by fluorescence in situ hybridization (FISH-LSI EGFR-Dual-colour-probe Vysis-Inc) as follows: tumor samples had a high EGFR-gene copy number if there was high polysomy ( 4-copies 40% of cells) or gene amplification (gene-clusters, gene/chromosome ratio per cell of 2, 15 copies of EGFR/ cell in 10% of cells) . The analysis of clinical data from all patients treated with Cetuximab (400–250mg/m 2 /w) and Irinotecan (300mg/m 2 /d1q21) was then performed. Results: EGFR-(IHC) high score was observed in 7pts from which only 2 had an objective response (OR). Intermediate (13pts) with 3 OR, low (12pts) with 1 OR and negative (8pts) with 2OR. Main FISH patterns were: high polisomy/amplification in 8pts with no response on cetuximab therapy. Low polisomy described in 19pts with 3 cases of disease remission. Disomy in 13pts with 5OR. No relationship was detected between IHC-score evaluation and FISH pattern. The clinical benefit (OR+stable disease =6months) was 65% in score-group 0–2; whereas 46% and 57% in groups 3–5/6–7 respectively, without statistical significance. Conclusion: According to our experience, IHC and FISH are unable to provide adequate selection criteria for the patients with different EGFR-status expression, who can benefit from Cetuximab therapy. No significant financial relationships to disclose.