[Prognostic marker profiles for risk of distant metastases in colorectal cancer]

In colorectal cancer (CRC) prognostic markers correlating with distant metastasis are of high clinical value. In recent years it could be demonstrated that sporadic CRC with microsatellite instability (MSI) exhibits a very low risk for distant spread. Within this group the medullary subtype represents a morphological prototype. In the new WHO classification other morphological variants, such as mucinous, signet ring cell, serrated, cribriform comedo type and solid-undifferentiated forms are graded according to their microsatellite status. The clinical value of BRAF mutations is also dependent on the microsatellite status. Recent data have shown an ambivalent prognostic impact of BRAF mutations. A BRAF mutation in combination with MSI is associated with a good prognosis, whereas a BRAF mutation in the background of microsatellite stability (MSS) indicates a very poor outcome. Based on the concept of migrating stem cells, combined high scores of CD133 and nuclear β-catenin expression can be additionally used as markers for a high risk of distant metastasis. Hence, an immunohistochemical algorithm can be defined by the combination of three markers (hMLH1, CD133 and β-catenin) which allows CRC with either a very high or a very low risk of distant spread to be identified.