3598 Background: First-line treatment of mCRC commonly utilizes FF+B. No reliable markers exist to predict clinical response to therapy. High-throughput genomic tumor screening may be of value to determine a genetic signature which predicts response to FF+B. Methods: All mCRC patients (pts) treated with first-line FF+B between 2000 and 2008 were independently reviewed for RECIST response. Formalin fixed paraffin embedded (FFPE) tumor samples underwent single blinded histopathologist review, microdissection with RNA extraction and hybridization to a CRC-specific microarray. Bioinformatic analysis was used to determine gene expression differences (GED) between responders (R) vs. nonresponders (NR). Principle component analysis (PCA) and hierarchical clustering (HC) were used to determine genomic relationships between R, NR, primary tumor (P) and metastases (mets). Results: 25 unique pts with 54 tumor specimens were processed. 88% (48/54) of FFPE had adequate RNA for analysis. More recent FFPE samples were associated with more successful RNA retrieval (p=0.053). FFPE age <36mo = 100% retrieval vs. 88% at 36-72mo vs. 60% >72mo. Under or over-GED were significant (sig) between P and site of mets including liver (79 genes; range -8.4 to +5.5 fold GED; p<0.05), lung (205 genes; range -6.1 to +110 fold GED; p<0.05), and ovary (117 genes; range -75 to +7 fold GED; p<0.05). There were no differences between R/NR in met site, Ki67% (median 53%), or microvessel density (MVD). HC identified a stringent gene listing (p<0.01; fold change >2) for R vs. NR. There were no differences between R/NR in primary MVD, but Ki67% was sig higher in R (66 vs. 35%; p=0.05). HC identified a stringent gene listing (p<0.01; fold change >2) for R vs. NR. Gene pathways involved in R/NR analysis include vascular development, angiogenesis regulation, and apoptosis. Representative GED products and ontology pathways are being analyzed. Conclusions: CRC microarray processing can be successfully conducted on historical FFPE, particularly if <72 mo old. Genomic profiling of P and mets confirm sig GED between met sites, R and NR, with confirmation testing of gene products ongoing. High Ki67 % in primary tumor may also predict response to FF+B.