The colorectal adenoma-carcinoma paradigm is well established and is responsible for over 70% of colorectal cancers (CRC), for both sporadic and hereditary types. The adenoma has also become the surrogate marker for prevention studies. The synchronous adenoma (SA) to sporadic cancers occur commonly, about 25%, and the associated clinical parameters have not been well studied. It is known to be associated with higher rates of adenoma recurrence, such as metachronous adenoma (MA), and second CRC. It is more likely to be proximal in location in the colon, microsatellite instable (MSI) and have a 20% better 5 year-survival than CRC without SA. All this information indicates that CRC+SA is biologically different than the usual CRC.
The aims of this study are to characterize SA in a well defined population of CRC and with respect to new CRC and MA. The molecular parameters with gene expression array analysis will be employed to answer some questions regarding: 1. Nature of adenoma to carcinoma development in sporadic CRC with and without SA. 2. Biological differences of proximal compared to distal CRC. 3. Significance of MSI in sporadic CRC. 4. Molecular basis for survival differences of CRC+SA, MSI instable CRC compared to the CRC without SA and MSI stable CRC. The methodology will involve collecting archival stored tissue of CRC and SA, laser microdissect out the tumor tissue and test it on gene microarray chip against genes of several categories: cell cycle, apoptosis, tumor suppressors, signal transduction, microsatellite markers, DNA repair, methylation and specific genes involved in tumorigenesis. These results will help our understanding of the adenoma, specifically the SA, and improve the use of this precursor in prevention studies. We will understand better the biology of different subsets of sporadic CRC, namely CRC+SA, proximal tumors and MSI instable tumors. Our findings will impact on future clinical therapeutic studies of CRC.
