Immunohistochemistry of colorectal carcinoma: current practice and evolving applications

The relatively high incidence of adenocarcinoma of the colon and rectum (colorectal carcinoma) in the general population makes its pathologic diagnosis one of the more frequent exercises in anatomical pathology. Although typically mundane in the primary setting, the correct identification of metastatic colorectal carcinoma or exclusion of metastatic disease from carcinoma arising in other anatomical foci can be problematic. The advent of targeted therapies and refinement of more traditional cytotoxic chemotherapeutic regimens mandates not only a more confident appraisal of site of origin but also assessment of those tumor-specific features that may alter therapeutic decisions. Despite the exponential increase in our understanding of the molecular pathogenesis of colorectal carcinoma, immunohistochemistry remains the foundation for resolution of these problematic cases and the number of antibodies available to the practicing pathologist continues to expand at a steady rate. In some cases, immunohistochemistry may also provide valuable prognostic information, either independently or as a surrogate marker for a specific route of carcinogenesis such as microsatellite instability. This review will focus on the use of new and more established immunohistochemistry markers in the diagnosis of colorectal carcinoma, with an emphasis on aberrant staining patterns of the various colorectal carcinoma subtypes as well as the utility of these markers in specific differential diagnostic settings.