Molecular Diagnostics of Colorectal Cancer

Context.-Of all gastrointestinal tract epithelial malignancies, molecular diagnostics has impacted colorectal cancer the most. Molecular testing can detect sporadic and inherited colorectal cancers that arise through the microsatellite instability pathway and can determine the efficacy of targeted drug therapy. Objectives.-To review the microsatellite instability pathway of colorectal carcinoma carcinogenesis and to demonstrate the diagnostic utility of molecular testing in the detection of patients with Lynch syndrome, an inherited disorder of this pathway. Also, to review the significance of detection of KRAS and BRAF gene mutations in predicting the response to anti-epidermal growth factor receptor therapies. Data Sources.-This article is based on original publications and review articles that are accessible through the PubMed biomedical database (US National Library of Medicine). Conclusions.-In modern pathology practice, molecular testing is a standard tool that is used to diagnose an inherited colorectal cancer predisposition syndrome (Lynch syndrome) and to help predict outcome and response to therapy for patients with advanced colorectal cancer. (Arch Pathol Lab Med. 2011;135:578-587)