Now that KRAS mutation testing is being recommended prior to receiving EGFR targeted inhibitors, especially the EGFR targeted monoclonal antibodies like cetuximab and panitumumab, how to perform the test is an issue that physicians (and patients) face. Most laboratories offering the test, including us, perform the test on tissue specimens (this can be a biopsy, lymph node, surgical specimen or metastatic lesion). The oncogenic KRAS activating mutations that result in resistance to EGFR targeted monoclonal antibodies arise in the tumor and are therefore not present in every cell in a person’s body. Several groups have looked for KRAS mutations in circulating DNA found in blood (specifically the plasma component) with mixed results. One study that compared KRAS mutations in codon 12 in lung cancer tissue and plasma from the same patient, found KRAS mutations in both tissue and plasma in 78% of cases (this was a small study of only 15 evaluable patients however). In another study comparing KRAS mutations in codon 12 in pancreatic tissue and plasma from the same patient, KRAS mutations were found in 60% of the tissue specimens but none of the plasma specimens (there were 30 specimens analyzed in this study).
Because the number of studies comparing different specimen types is still limited, it is difficult to draw meaningful conclusions about the accessibility of detecting KRAS mutations in non-tissue specimens. Perhaps pancreatic tumors and lung tumors are inherently different in the amount of tumor DNA that they release into the system. Until these issues are more fully investigated, the most accurate way currently to look for the presence of a KRAS mutation is in a person’s tumor tissue. However, TMD will be happy to participate in or help plan a pilot study to examine KRAS mutations in blood specimens, if this is of interest.