Background: Mutations in the KRAS gene occur at an early stage in the development of colorectal carcinoma. Importantly, KRAS mutation predicts resistance to anti-epidermal growth factor receptor therapy in stage IV disease. Goals: The aim of the current study is to correlate histologic features of colon cancer with the presence of KRAS mutations. Study: Tumor tissue from 145 colon cancer resections was tested for KRAS mutations. KRAS mutation status was correlated with demographic and histologic characteristics. Statistical analysis was performed using the Pearson &khgr;2 test and multivariate analysis. Results: KRAS mutations were present in 55/145 cases (37.9%), consistent with reported rates. KRAS mutations were significantly associated with usual adenocarcinoma morphology (multivariate P=0.014), peritumoral lymphocytic response (&khgr;2, P=0.028; multivariate P=0.017), T3-T4 status (&khgr;2, P=0.012; multivariate P=0.015), right-sided location (multivariate P=0.027), absence of lymphovascular invasion (multivariate P=0.008), and metastases at the time of resection (multivariate P=0.034). No association was found between KRAS mutation status and other factors. Conclusions: Specific morphologic features in colon cancer suggest a higher likelihood of the presence of KRAS mutations. These morphologic features overlap partially with those associated with DNA mismatch repair gene mutations. If confirmed, these results may suggest a paradigm for directed KRAS testing.
A. Gunal, P. Hui, S. Kılıç
Journal of Clinical Gastroenterology