Discordance of KRAS mutational status in a single colonic resection specimen in a patient with colorectal cancer: A case report and review of the literature

Evaluation for mutation within the KRAS oncogene as a determinant for the use of either cetuximab or panitumumab, the monoclonal antibodies that are directed against endothelial growth factor receptor (EGFR), is the first individualized treatment for patients with metastatic colorectal cancer. Although not absolute, concordance of the mutational status among different cancer sites in an individual patient is high enough that the clinical practice consensus is for only a single site to be assessed for this mutation, be it primary tumor or a single metastasis. Here, we report a unique case of discordance between KRAS mutational statuses within 3 separate foci of adenocarcinoma contained within a single surgical colonic resection. It is most likely that these foci represent 3 separate simultaneously emerging adenocarcinomas in a patient who likely has familial adenomatosis polyposis. The patient's metastatic disease was resistant to both EGFR monoclonal antibodies, suggesting that his recurrent metastatic disease was KRAS mutated and probably was derived from one of the similarly mutant foci. In summary, concordance of KRAS mutational status should not be assumed to be absolute among all disease sites. Although it is not always practical or necessary to assess this status from multiple sites of disease, certain patients, particularly those who may have more than 1 primary tumor or whose primary tumor is KRAS wild type, may benefit from KRAS mutational reassessment at multiple metastatic sites before initiation of therapy with an EGFR monoclonal antibody .