Pathologic Evaluation of Therapeutic Biomarkers in Colorectal Adenocarcinoma

Molecular testing is an essential component of the pathologic evaluation of colorectal carcinoma providing diagnostic, prognostic, and predictive therapeutic information. Mismatch repair status evaluation is required for all tumors. Advanced and metastatic tumors also require determination of tumor mutational burden, KRAS, NRAS, and BRAF mutation status, ERBB2 amplification status, and NTRK and RET gene rearrangement status to guide therapy. Multiple assays, including immunohistochemistry, microsatellite instability testing, MLH1 promoter methylation, and next-generation sequencing, are typically needed. Pathologists must be aware of these requirements to optimally triage tissue. Advances in colorectal cancer molecular diagnostics will continue to drive refinements in colorectal cancer personalized therapy.