Identification of subtypes in colorectal cancer and their prognostic values

Abstract

4041 Background: The discovery and widespread acceptance of molecular subtypes in breast cancer has changed the way that this disease is viewed. Similarly, we have focussed on stage II colorectal cancer where 20–25% of patients are at risk of recurrent disease following surgery. There are currently several types of colorectal cancer recognised by histopathological methods, however, little has been published regarding disease classification at a molecular level. Methods: We have taken an unbiased approach to the molecular classification of colorectal cancer. Using a colorectal cancer disease specific microarray platform we have performed expression profiling and bioinformatic analysis of 500 formalin fixed and paraffin embedded (FFPE) stage II colorectal cancer samples, in order to identify and characterise molecular subtypes. Results: We have identified molecular subtypes for colorectal cancer. One of these subtypes is enriched with tumours with microsatellite instability (MSI) that are predominantly proximal, mucinous and poorly differentiated. It is notable that while MSI is generally accepted to be associated with a good prognosis, we have found both good and poor prognosis patients within this subtype. A second subtype contains tumors with a low CpG island methylator phenotype. Another subtype is defined by an expression pattern consistent with activation of tumor suppressors. The remaining subtypes are newly identified. Conclusions: We have identified molecular subtypes in colorectal cancer. We will present how knowledge about these subtypes may affect patient management and may be used to guide the development of novel therapeutic strategies. [Table: see text]