Abstract 5551: Somatic mutations in KRAS, BRAF and PIK3CA genes in Chilean patients with sporadic colorectal cancer: Correlation with clinical and histological features

Abstract

Abstract Background: KRAS, BRAF and PIK3CA proto-oncogenes encode for proteins involved in epidermal growth factor receptor (EGFR) signaling pathways. Activating mutations in these genes may contribute to tumor development and induce resistance to biological therapies in patients with metastatic colorectal cancer (CRC). Furthermore, microsatellite instability (MSI) has been proposed as a prognostic and predictive marker in sporadic CRC. Patients and methods: In tumors of patients undergoing surgery for sporadic CRC at our institution, somatic mutations in KRAS, BRAF and PIK3CA genes were assessed by single-strand conformation polymorphism(SSCP) and direct sequencing. MSI analysis was performed using the 5 markers of the standard NIH panel. Clinical and histopathological data of the patients were obtained from our prospectively maintained database. Results: A total of 58 patients with a nearly equal gender distribution and a mean age of 62 years were included. A total of 31 mutations in 26 patients were identified. The frequency of mutations was 28% for KRAS, 9% for BRAF and 17% for PIK3CA. No difference was found in the mutation frecuency between the different tumor locations (42,1% in right colon vs. 46,2% in left colon/rectum, P= NS) or lymphnode status (37,5% in node positive vs. 50% in node negative tumors, P=0,346). Tumors with deeper invasion showed a higher frecuency of mutations, but this tendency did not reach statistical significance (32% in pT1-2 vs. 51% in pT3-4, P=0,157). In 26% of the patients, MSI-high was observed, more frecuently in tumors of the right colon (57,9% vs 10,3%, P<0,001). Patients with BRAF mutations, a higher proportion of MSI-high was found compared to BRAF wildtype (27% vs. 2,3%, P=0,013). There was no correlation between the lymphnode positivity and MSI status. Conclusion: Our results show that the frequency of mutations in patients with sporadic CRC in Chile is similar to that described in other countries. The presence of MSI-high is correlated with tumors in the right colon and with mutations in the BRAF gene. The tendency of finding more mutations in locally advanced and node-negative tumors needs to be confirmed in future studies with a larger number of patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5551. doi:1538-7445.AM2012-5551