Defining a molecularly normal colon

As techniques evolve that allow molecular characterization of disease proce sses such as cancer, definition of "normal" at a molecular level becomes in creasingly important. Increasingly large numbers of mutations are found at the genomic level, but whether all of those mutations contribute to the mal ignant state of a carcinoma cell is not clear. Without knowledge of what co nstitutes normality on the proteomic level in an organ or cell, we cannot d etermine what genomic changes are physiologically important. Traditionally, colon cancer is identified and classified by histological criteria. Margin s of the colon are defined as "grossly uninvolved" when the histology is in distinguishable from that of normal (free from disease) colon. By using mol ecular pathology techniques and working backward from colon adenocarcinoma to hypoplastic polyps to presumably normal mucosa, we defined some of those protein differences. Our results may provide a molecular basis for identif ying tumor formation and progression in situ.