Molecular staging of colorectal cancer

PURPOSE. Multiple attempts have been made to improve the clinical/pathologic staging system of Dukes to focus adjuvant therapy decisions. The purpose of this study was to determine whetherK-ras mutational status of regional nodes in patients with Dukes B₂ colorectal cancer could be used to stage their disease more accurately. METHODS: Using formalin-fixed, paraffin-embedded archival material, tumor samples were screened forK-ras mutations using a mutation-specific polymerase chain reaction method, followed by gel electrophoresis in a 96-well array. Patients with Dukes B₂ tumors that have mutations in codon 12 or 13 of theK-ras gene were identified. RESULTS: Mutational analysis of the lymph nodes from these patients revealed an 80 percent (16/20) incidence of the same mutations in regional lymph nodes. None of the four patients with mutation-free nodes developed recurrence compared with 37.5 percent (6/16) withK-ras positive lymph nodes. CONCLUSIONS: The data suggest that patients with Dukes B₂ colorectal cancers that have mutations in codon 12 or 13 of theK-ras gene are at high risk for the development of nodal metastases. Mutational analysis of the lymph nodes identifies high-risk patients who should be considered for adjuvant chemotherapy. Therefore,K-ras mutational analysis should be considered for molecular staging of colorectal cancer.This work was done at the Ferguson-Blodgett Digestive Disease Institute, Grand Rapids, Michigan.Financial support came from the Ferguson-Blodgett Foundation.Read at the meeting of The American Society of Colon and Rectal Surgeons, Philadelphia, Pennsylvania, June 22 to 26, 1997.