Colorectal cancer is the second-leading cause of cancer death in the USA, with more than 155,000 predicted new cases per year. Recently in specimens from consecutive patients, imaging MALDI (IMS) demonstrated chemical evidence of two proteins, gi|119592539 hCG1787564 [Homo sapiens] Mass: 57590, and gi|119592490 hCG2040674 [Homo sapiens] Mass: 108178 in colon adenocarcinoma and in histopathologically normal satellite tissue. This finding may represent a potential marker for field cancerization or a field defect, e.g., age-related hypermethylation in normal colonic mucosa. Such alterations result in microsatellite instability, and synchronous and metachronous lesions which develop into cancers. Therefore, the use of histopathology alone may significantly affect therapy by underestimating the extent of metaplastic or malignant disease. We hypothesized that in comparison to conventional histopathology, using proteomic classification IMS can better identify the extent of metaplastic disease beyond the recognized tumor.

The combination of high pressure protein extraction with organic solvent and LCMS increased the yield of peptides obtained from the tissue digest and identification of heretofore unidentified proteins. The protein mass numbers are used to reconstruct the IMS images, and localize the proteins in tissue

The presence of variation in polyp proteins in the biopsy tissue strongly suggests genetic field differences, which may be predictive of carcinoma not only developing in these polyps, but at other sites in the colon as synchronous and metachronous lesions. These findings may alter the current paradigm of histopathology tissue diagnosis for tumor and require examination of the biopsy tissue with histopathology and mass spectrometry for complete diagnosis.