The Prognostic Value of c-Kit, K-ras Codon 12, and p53 Codon 72 Mutations in Egyptian Patients With Stage II Colorectal Cancer

BACKGROUND: The prognosis for patients with colorectal cancer (CRC) depends mainly on standard clinicopathologic factors. However, patients with similar disease characteristics exhibit various outcomes, especially in stage II. Therefore, the identification of molecular prognostic markers is needed to predict patient outcomes. METHODS: The authors assessed the prognostic value of c-Kit (also called cluster of differentiation 117 [CD117] or KIT), cyclooxygenase-2 (COX-2), tumor protein 53 (p53), and Kirsten rat sarcoma viral oncogene homolog (K-ras) aberrations in 90 patients with stage II CRC using immunohistochemistry and molecular techniques. The results were correlated with standard clinicopathologic prognostic factors, overall survival (OS), and disease-free survival (DFS). RESULTS: COX2 and c-Kit overexpression was detected in 54.6% and 59.3% of patients, respectively. Overexpression of p53 was detected in 47 patients, including 29 who had mutations, and a unique mutation pattern was detected with 3 hotspots at codons 72, 245, and 273. Overexpression of ras was detected in 44 patients, including 37 who had mutations. On multivariate analysis, c-Kit overexpression, p53 codon 72 mutations, perforation, and performance status were independent prognostic factors for DFS (P = .054, P = .015, P < .0001, and P = .043, respectively); whereas codon 12 K-ras mutation, performance status, and perforation were independent prognostic factors for OS (P = .033, P = .006, and P < .0001, respectively). CONCLUSIONS: The current results provide evidence for the prognostic value of c-Kit overexpression in patients with stage II CRC. The high p53 mutation rate and the unique hotspot in codon 72 have not been reported previously in CRC. This may be related to environmental or racial features that are unique to the studied population. Cancer 2010;116:4954-64. (C) 2010 American Cancer Society