Abstract 2264: K-ras mutations in colorectal cancer may predict a pattern of organ-specific metastasis

Abstract

Abstract Background: Activating mutations of the K-ras oncogene in colorectal cancer (CRC) are associated with resistance to EGFR antibodies and poor prognosis. We systematically analyzed clinical and pathological characteristics associated with K-ras mutations. Methods: Patients with CRC referred to the phase I program for targeted therapy were analyzed for K-ras mutations using PCR-based DNA sequencing. Patients with mutant K-ras were matched with wild-type (wt) K-ras controls. Multiple clinical and pathological characteristics were analyzed to determine, whether there is a phenotype associated with K-ras mutations. Results: A total of 151 patients with CRC were identified; 61 with K-ras mutations; 80 with wt K-ras and 10 with unknown K-ras status. Patients with K-ras mutations compared with wt K-ras had more frequently lung metastases (80% vs. 63%, p = 0.03). Patients whose tumors had K-ras mutations had higher number of metastatic sites of disease (3.18 vs. 2.65; p = 0.013). There were no associations between K-ras mutations and gender, age at diagnosis, liver metastases, peritoneal metastases, lymphatic involvement or Duke stage at diagnose. Patients with K-ras wt had a trend for longer median survival (283 vs. 222 weeks, p=0.09). There was no difference in the median survival from diagnosis in patients with different types of K-ras mutations (codon 12, codon 13, and codon 61). Dukes staging was the only statistically significant prognostic factor on multivariate analysis (p < 0.05). Conclusions: K-ras mutations in CRC in comparison with wt K-ras were associated with more frequent lung metastases and shorter survival. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2264. doi:10.1158/1538-7445.AM2011-2264