Use of gene expression profiling to determine prognosis and therapeutic targets for patients with appendiceal carcinoma.

418 Background: Appendiceal carcinomas are rare neoplasms that often present as peritoneal surface malignancies. The tumors are treated similarly to primary colorectal metastases, despite having different biological environments. The aim of this study is to utilize genomic analyses to understand the underlying biology of appendiceal carcinoma in order to better guide prognosis and therapy. Methods: Forty-one metastatic human tumors to the peritoneum (26 appendiceal carcinoma, 15 colorectal carcinoma) were subjected to global gene expression analysis. Unsupervised hierarchical clustering was used to differentiate phenotypes based on differential gene expression. Phenotypes were further analyzed to find differences in oncogenic pathway deregulation and findings were validated using gene specific inhibitors in vitro. Results: Unsupervised hierarchical clustering revealed three distinct phenotypes, two consisting of predominantly low grade appendiceal samples (Cluster 1 and Cluster 2) and one consisting of pr...