Immunohistochemistry of colorectal carcinoma: current practice and evolving applications

Summary

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.

Introduction

Despite the availability of preventative screening, colorectal carcinoma (CRC) remains one of the most commonly diagnosed malignancies even in the developed world. It is the second most commonly diagnosed malignancy in males and third in females and ranks fourth and third as a cause of cancer-related death in these groups, respectively [1]. The continued refinement of traditional cytotoxic therapeutic regimens, as well as our more thorough understanding of the molecular pathogenesis of cancer in general, has made a “one size fits all” approach to treatment increasingly anachronistic, and the treatment of CRC is no exception. Translation of this apperception into optimal treatment for the individual patient is dependent not only on correct identification of the primary site but also on accurate assessment of individual site-specific tumor characteristics that might affect the timing or selection of different treatment regimens. For CRC in particular, although death rates have been declining in the Western world, traditional staging has proven less than optimal for the selection of those patients who would be most likely to benefit from first-line adjuvant chemotherapy.

It is increasingly clear that the pathogenesis of CRC is heterogeneous at the molecular level, and such differences appear to influence behavior and dictate the likelihood of response to both traditional cytotoxic and newer, often expensive targeted therapeutic agents. It is therefore incumbent upon pathologists to provide accurate histologic assessment to our colleagues in oncology and surgery to identify not only the site of origin but also those site-specific features that may impact treatment decisions. The objective of this review is to provide pathologists with a synopsis of the various immunohistochemistry (IHC) markers useful for the diagnosis of CRC, including elaboration on CRC subtypes that may exhibit “aberrant” staining patterns (Table 1) and the differential staining patterns of other primary sites (Table 2). Because IHC results are dependent on a myriad of technical factors and interpretation parameters, the tabulated information represents a combination of information within the literature and personal experience. Where relevant, potential prognostic or predictive significance and molecular interrelationships will also be briefly discussed.