Tumor Location Is Associated With the Prevalence of Braf And Pik3ca Mutations in Patients with Wild-Type Ras Colorectal Cancer: A Prospective Multi-Center Cohort Study in Japan |
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| Affiliation: | 1. Department of Clinical Oncology, Aichi Cancer Center, Nagoya, Japan;2. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan;3. Division of Surgical Oncology, Department of Surgery, Nagoya Graduate School of Medicine, Nagoya, Japan;4. Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan;5. Department of Surgery, Nagoya Medical Center, Nagoya, Japan;6. Department of Surgery, Meitetsu Hospital, Nagoya, Japan;7. Department of Medical Oncology, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan;8. Department of Surgery, Tosei General Hospital, Seto, Japan;9. Department of surgery, Fujita Health University, Toyoake, Japan;10. Department of Medical Oncology, Kainan Hospital, Yatomi, Japan;11. Department of surgery, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan;12. Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Science, Nagoya, Japan;13. Department of Surgery, Yokkaichi Municipal Hospital, Yokkaichi, Japan;14. Department of Gastroenterological Surgery, Aichi Cancer Center, Nagoya, Japan;15. Department of Endoscopy, Aichi Cancer Center, Nagoya, Japan;p. Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan |
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| Abstract: | BACKGROUND: Primary tumor location is a critical prognostic factor that also impacts the efficacy of anti-epidermal growth factor receptor (EGFR) therapy in wild-type RAS (KRAS/NRAS) metastatic colorectal cancer (CRC). However, the association between the incidence of BRAF and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations and primary tumor location remains unclear. METHODS: We prospectively collected tumor samples and clinical data of patients from 15 hospitals between August 2014 and April 2016 to investigate RAS, BRAF, and PIK3CA mutations using a polymerase chain reaction-based assay. According to the primary tumor location, patients were classified to right-sided (from cecum to splenic flexure) and left-sided (from descending colon to rectum) tumor groups. RESULTS: In total, 577 patients with CRC were investigated, 331 patients (57%) had CRC with wild-type RAS; of these 331 patients, 10.5%, 4.8%, and 5.9% patients harbored BRAFV600E, BRAFnon-V600E, and PIK3CA mutations, respectively. BRAF/PIK3CA mutations were more frequent in females, patients with right-sided tumors, and patients with peritoneal metastasis cases and less frequent in patients with liver metastases. The prevalence rates of BRAFV600E and PIK3CA mutations were higher in patients with right-sided tumors than in those with left-sided tumors (32.3% vs. 4.8% and 17.2% vs. 3.6%, respectively). CONCLUSIONS: More than half of the patients with right-sided CRC and wild-type RAS harbored BRAF/PIK3CA mutations, including BRAFnon-V600E, which may contribute to the difference in the anti-EGFR efficacy between the right- and left-sided CRC. |
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