Abstract 2351: Evaluation of KRAS and BRAF mutation analysis in primary metastatic colorectal cancers versus matched syn- and metachronous metastases

Abstract

Abstract Background: The KRAS mutation status was shown in recent studies to be a predictive biomarker for anti-EGFR monoclonal antibody (mAB) therapy in metastatic colorectal cancer (mCRC). Patients without KRAS mutations (wild type KRAS) did benefit from anti-EGFR-mAB therapy whereas patients with tumors bearing a KRAS mutation did not benefit from this targeted therapy. KRAS mutation analysis is thus required before anti-EGFR-mAB treatment in all mCRCs. As published in the clinical studies, primary tumors are commonly used as the standard tissue. However, KRAS mutation analysis is often complicated because primary tumors are being discarded by many institutes of pathology years after diagnosis. Instead recent metastases are available and are used for KRAS mutation analysis. However the question is raised if primary tumors and metastases are equally informative regarding the KRAS and BRAF mutation status especially when considering the multiple steps during tumor cell dissemination and metastatic processes. So far only little and heterogeneous data are available about this issue. Patients and methods: To address this question we performed a KRAS mutation analysis (codons 12, 13, 61) in 111 colorectal cancers and 171 matched metastases in lymph nodes, liver, lung, ovary, peritoneum, brain, urinary bladder and bone. Additionally, BRAF mutation analysis was done in all KRAS wild type tumors. In addition, multiple (>=2) matched synchronous or metachronous metastases and corresponding primary tumors were analysed in 44 cases. KRAS and BRAF mutation analysis was done using pyrosequencing technology. Tumor cells were gained either by microscopically controlled manual microdissection or by laser assisted microdissection. Results: Primary tumors and matched metastases with initially discrepantly appearing KRAS mutation status were re-analysed using laser-microdissection. By means of laser microdissection we finally did not find any discrepancies in the KRAS and BRAF mutation status in primary tumors versus matched syn- or metachronous metastases. Conclusion: KRAS and BRAF mutation analysis in metastases appears to be as valid as in primary tumors and should serve as reliable specimens in cases where primary tumors are not available to predict response to therapies with anti-EGFR targeted monoclonal antibodies in metastatic colorectal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2351.