Relationship between oncogenic mutations (RAS, BRAF and PIK3CA) and tumor location and prognosis in colorectal cancer.

Authors

null

Daisuke Inagaki

Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan

Daisuke Inagaki , Manabu Shiozawa , Tetta Satoyoshi , Yosuke Atsumi , Masaaki Murakawa , Keisuke Kazama , Akio Higuchi , Naoto Yamamoto , Soichiro Morinaga , Yasushi Rino , Munetaka Masuda , Yohei Miyagi

Organizations

Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan, Department of Surgery, Yokohama City University, Yokohama, Japan, Kanagawa Cancer Center, Yokohama, Japan, Division of Hepatobiliary and Pancreatic Surgery, Kanagawa Cancer Center, Yokohama, Japan, Division of Molecular Pathology and Genetics, Kanagawa Cancer Center Research Institute, Yokohama, Japan

Research Funding

Other

Background: Several studies have reported that right-sided colon cancers (RCC) and left-sided colorectal cancers (LCRC) differ in several factors including genetic features. We investigated the difference in clinicopathological characteristics and oncogenic mutation status between patients with RCC and LCRC in all stages and assessed outcome. Methods: This study was a prospective, observational study. Patients were recruited from November 2014 to February 2016. Formalin-fixed paraffin-embedded tissue blocks were collected and DNA wes extracted from tissue sections from 227 cases. There was no double cancer. Mutations in KRAS, NRAS, HRAS, BRAF and PIK3CA were detected by next-generation DNA sequencer. Tumors from cecum to transverse colon were defined as RCC, and tumors from descending colon to rectum were defined as LCRC. The median follow-up period was 521 days. Results:KRAS, NRAS, BRAF and PIK3CA mutations were present in 95 patient (41.9%), 7 patients (3.1%), 10 patients (4.4%) and 23 patients (10.1%) respectively, and there was no HRAS mutation in all patients. RCC was 68 patients and LCRC was 159 patients. Poorly differentiated adenocarcinoma and mutinous adenocarcinoma were significantly more frequent in RCC compared to LCRC (P = 0.031). KRAS mutations were detected in 37 patients with RCC (54.4%) and in 58 patients with LCRC (36.5%). BRAF mutations were detected in 7 patient with RCC (10.3%) and in 3 patients with LCRC (1.9%). KRAS and BRAF mutation in RCC were significantly more frequent than in LCRC (P = 0.012 and P = 0.005, respectively). The incidence of NRAS and PIK3CA mutation was no difference between two groups. In all patients, overall survival was evaluated. On univariate Cox regression analysis, BRAF mutation was associated with significantly poorer overall survival than BRAF wild type (HR = 4.831, P = 0.013). Other oncogenic mutation status and tumor location weren’t associated with overall survival. Conclusions:KRAS and BRAF mutation were more frequent in the patients with RCC compared to those with LCRC in all stages. This study suggested BRAF mutation correlated with poor outcomes in patients with colorectal cancer.

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Abstract Details

Meeting

2017 ASCO Annual Meeting

Session Type

Publication Only

Session Title

Publication Only: Gastrointestinal (Colorectal) Cancer

Track

Gastrointestinal Cancer—Colorectal and Anal

Sub Track

Epidemiology/Outcomes

Citation

J Clin Oncol 35, 2017 (suppl; abstr e15109)

DOI

10.1200/JCO.2017.35.15_suppl.e15109

Abstract #

e15109

Abstract Disclosures

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