Molecular staging of colorectal cancer - K-ras mutation analysis of lymph nodes upstages Dukes B patients

PURPOSE. Multiple attempts have been made to improve the clinical/pathologi c staging system of Dukes to focus adjuvant therapy decisions. The purpose of this study was to determine whether K-ras mutational status of regional nodes in patients with Dukes B-2 colorectal cancer could be used to stage t heir disease more accurately. METHODS: Using formalin-fixed, paraffin-embed ded archival material, tumor samples were screened for K-ras mutations usin g a mutation-specific polymerase chain reaction method, followed by gel ele ctrophoresis in a 96-well array. Patients with Dukes B-2 tumors that have m utations in codon 12 or 13 of the K-rns gene were identified. RESULTS: Muta tional analysis of the lymph nodes from these patients revealed an 80 perce nt (16/20) incidence of the same mutations in regional lymph nodes. None of the four patients with mutation-free nodes developed recurrence compared w ith 37.5 percent (6/16) with K-ras positive lymph nodes. CONCLUSIONS: The d ata suggest that patients with Dukes B-2 colorectal cancers that have mutat ions in codon 12 of 13 of the K-rns gene are at high risk for the developme nt of nodal metastases. Mutational analysis of the lymph nodes identifies h igh-risk patients who should be considered for adjuvant chemotherapy. There fore, K-ras mutational analysis should be considered for molecular staging of colorectal cancer.