Primary tumor location is an important predictive factor for KRAS/NRAS wild-type colorectal cancer treated with anti-EGFR therapy. BRAF and PIK3CA mutations are also known to affect a response in anti-EGFR therapy. However, the relationship between the prevalence of BRAF/PIK3CA mutations and the location of the primary site is still unclear.
We prospectively collected tumor samples and clinical data from colorectal cancer patients in 14 hospitals and investigated KRAS/NRAS/BRAF/PIK3CA gene mutations, including 33 types of BRAF non-V600E mutations, using a PCR-based multiplex kit.
As of April 30, 2015, a total of 545 CRC patients were enrolled, and 313 patients (57%) revealed KRAS/NRAS wild-type cancer. Patient characteristics included: median age, 65 (range, 30–90); male/female, 60%/40%; clinical stage I-III/IV, 15%/85%; and location of primary site, right-sided colon/left-sided colon/rectum, 23%/30%/47%. The prevalence of BRAF V600E/BRAF non-V600E/PIK3CA mutations were 10.1%, 4.7% and 5.9%, respectively. The detected BRAF non-V600E mutations were G466E, G469A, N581T, D594G, T599_V600insT, V600R, K601E and K601N. All mutations were mutually exclusive. In RAS wild-type cancer patients, BRAF/PIK3CA mutations were more frequent in female (p = 0.0029), right-sided (p = 0.0001) and peritoneal metastasis (p = 0.0016) cases and less frequent in cases presenting liver metastasis (p = 0.0041). In RAS wild-type right-sided cancers, the prevalence of BRAF V600E/ BRAF non-V600E/PIK3CA mutations were 31.7%, 8.1% and 19.2%, while in left-sided colon and rectum cancers, they were 4.6%, 2.5% and 3.6%, respectively.
More than half of RAS wild-type right-sided colon cancer patients have BRAF/PIK3CA mutations, including BRAF non-V600E. The existence of these mutations may affect anti-EGFR efficacy between right- and left-sided colorectal cancers.
Clinical trial identification
Legal entity responsible for the study
Aichi Cancer Network
All authors have declared no conflicts of interest.