Introduction. Colorectal cancer (CRC) is the second leading cause of cancer related deaths, due to the development of distant metastases in many CRC patients. To detect metastatic disease in early stage, the identification of tumor cells circulating in the peripheral blood of patients (CTCs) is of outmost importance. Several techniques have recently been developed which can detect CTCs, two of them are the CellSearch® system and the EpiSpot assay.

We have investigated genomic aberrations and gene expression patterns in primary colorectal tumors in correlation with CTC status of patients. This may lead to the identification of the underlying mechanisms of metastatic spread and potential new markers for detecting the tumor's capability to disseminate.

Methods. Peripheral blood of 48 colorectal patients was investigated by CellSearch® and EpiSpot for CTCs. Samples with at least one CTC, detected with either the CellSearch® system or the EpiSpot assay were considered as positive. Genomic DNA and mRNA extracted from the primary tumors of the same patients were investigated with Illumina based Comparative Genomic Hybridization (CGH) and Gene Expression profiling (GEP) microarrays. CGH arrays covered the whole genome with an average resolution of 5kb and GEP arrays covered more than 25,000 annotated genes.

Results. Twenty-nine patients were diagnosed to be positive for CTCs, either with the EpiSpot assay or the CellSearch® system; negative for CTCs in both assays were 17 blood samples. Array-CGH showed that primary tumors from CTC positive patients harbored significantly more often loss of chromosome 15q11 (Fisher's exact test, p<0.01). The Significance Analysis of Microarrays (SAM) revealed 13 genes to be differentially expressed between both groups. These genes are mainly involved in kinase activity and ATP-binding, and are located in the plasma membrane. Furthermore, CYFIP1 was downregulated in colorectal tumors from CTC positive patients compared with CTC negative patients which correlated with its loss detected with array-CGH. CYFIP1 is a known putative invasion suppressor gene in epithelial cancers.

Conclusion. Our results suggest that several molecular and genomic profiles can be identified as marker for tumor cell dissemination in CRC. More over, significant correlation between CTC status and the primary tumor's genomic profile indicates a biological rationale for tumor cell dissemination rather than a random effect or shedding of cells.

Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2165.