Recent developments have led to the recognition that KRAS testing on tumor tissue is required for colorectal cancer patients who are eligible for EGFR blocking therapy. Therefore the European Society of Pathology (ESP) has decided to start a helpdesk and a quality assurance program for KRAS testing in colorectal cancer. A joint committee of the Working Groups for molecular pathology and diseases of the gastrointestinal tract has prepared a manuscript on this topic, which is already published in Virchow Archiv. The ESP aims to have the helpdesk, and to have the external quality assurance program.
Novel therapeutic agents targeting the epidermal growth factor receptor (EGFR) have improved outcomes for patients with colorectal carcinoma. However, these therapies are effective only in a subset of patients. Activating mutations in the KRAS gene are found in 30-40% of colorectal tumors and are associated with poor response to anti-EGFR therapies. Thus, KRAS mutation status can predict which patient may or may not benefit from anti-EGFR therapy. Although many diagnostic tools have been developed for KRAS mutation analysis, validated methods and standardized testing procedures are lacking. This poses a challenge for the optimal use of anti-EGFR therapies in the management of colorectal carcinoma. Here we review the molecular basis of EGFR-targeted therapies and the resistance to treatment conferred by KRAS mutations. We also present guideline recommendations and a proposal for a European quality assurance program to help ensure accuracy and proficiency in KRAS mutation testing across the European Union.
H Van Krieken
March 2009
Contact
Home