title: RAS mutation is a prognostic biomarker in colorectal cancer patients with metastasectomy.
abstract: Studies have demonstrated a relationship between clinical outcomes after curative resection for colorectal cancer (CRC) and gene mutations of the EGFR pathway; however, no studies have examined metastatic CRC (mCRC) patients with metastasectomy. The aim of this study was to evaluate the relationship between gene mutations of EGFR pathway and clinical outcomes after metastasectomy in mCRC patients. A total of 1,053 patients histopathologically confirmed CRC received a genotyping test for the EGFR pathway from February 2012 to October 2013. Detailed information was obtained through review of medical records. Gene mutations of EGFR pathway were analyzed by Luminex assay. Overall survival (OS) and recurrence free survival were estimated by the Kaplan-Meier method and the log-rank test was used to compare the survival outcomes by gene mutation status. A total of 132 patients received metastasectomy. The frequencies of KRAS exon 2, KRAS exon 3.4, NRAS, BRAF, and PIK3CA mutations were 38.6% (51/132), 3.6% (5/132), 5.1% (7/132), 5.1% (7/132), and 8.7% (12/132), respectively. With a median follow-up of 84.1 months (57.2-NA) for a survivor, the 4-year OS rate was 65.6% for mCRC with RAS mutation, and 81.3% for mCRC with wild-type RAS (p < 0.05). We observed a statistically significant correlation for only the RAS mutation and OS. In multivariate analysis, RAS mutation and liver metastasis were independent factors for shorter OS. There were no significant differences between gene mutations of EGFR pathway and recurrence free survival. RAS mutation in mCRC metastasectomy patients was associated with shorter overall survival.
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Osumi
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Shinozaki
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Mitsukuni
authors.initials: M
authors.lastname: Suenaga
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsusaka
authors.affiliation: Department of, Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Konishi
authors.affiliation: Department of, Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Akiyoshi
authors.affiliation: Department of, Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Fujimoto
authors.affiliation: Department of, Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nagayama
authors.affiliation: Department of, Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Fukunaga
authors.affiliation: Department of, Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Ueno
authors.affiliation: Department of, Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Mise
authors.affiliation: Department of, Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Takeaki
authors.initials: T
authors.lastname: Ishizawa
authors.affiliation: Department of, Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Department of, Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of, Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Saiura
authors.affiliation: Thoracic Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Hirohumi
authors.initials: H
authors.lastname: Uehara
authors.affiliation: Thoracic Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Mingyon
authors.initials: M
authors.lastname: Mun
authors.affiliation: Thoracic Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Sakae
authors.initials: S
authors.lastname: Okumura
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Mizunuma
authors.affiliation: Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Miki
authors.affiliation: Department of, Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yamaguchi
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D005091:Exons; D005260:Female; D005787:Gene Frequency; D011905:Genes, ras; D005838:Genotype; D006801:Humans; D008297:Male; D059146:Metastasectomy; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D012008:Recurrence; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor
keywords: RAS mutation; biomarker; metastasectomy of colon cancer; repeat metastasectomy