MPECS to detect high risk colorectal adenomas

Colorectal cancer (CRSC) is one of the leading cancers and the mortality is high and hardly has changed over the past decades. It is believed that most CRCs are preceded by a pre-invasive phase, called colorectal adenoma (CRA). About 2-5% of all CRAs pro gress to cancer. It is therefore important to have accurate identifiers of metachronous cancer risk in CRAs, but current methods (number of polyps, polyp size, dysplasia grade and histologic type) are inaccurate. The number of studies targeting CRAs for the analysis of metachronous risk factors is limited, due to the fact that follow-up time must be long and the number of patients large (due to the relative low frequency of cancers in CRAs). We have collected before nearly 8000 polyps, and unpublished r esults have shown that a morphometrically defined Monotonous Population of Elongated Cells (MPECS) in ColoRectal Adenomas (CRAs) is much stronger predictive of metachronous cancer (Hazard ratio=HR=54, positive predictive value 20%, sensitivity 100%, negat ive predictive value 100%) than classical features (HR1.5-3). The current research project aims to analyze a series of routinely diagnosed 21000 biopsies of CRAs, to validate these potentially important results. If confirmed, this may drastically prevent under-and overtreatment of CRA patients, and save large amounts for the national health care system. MPECS may then be used as surrogate intermediate endpoint biomarkers (SEBS) for detecting a specific protein profile using proteomics. Soluble proteins a lso may be detected in blood and sputum, thereby opening the possibility for population screening and perhaps even vaccination to prevent CRAs and perhaps also CRCs. Possible implications of the research results are: 1. Implementation in diagnostic patho logy routine and 2. Possibly in clinical gastro-enterologic decision making. 3. Early etection of CRAs by proteomics. Dr. Baak is professor-2 of pathology, Univ. of Bergen, position accepted 16-06-2004.