TY - JOUR
T1 - BRAF V600E mutation is a predictive indicator of upfront chemotherapy for stage IV colorectal cancer
AU - Morikawa, Tatsuya
AU - Inada, Ryo
AU - Nagasaka, Takeshi
AU - Mori, Yoshiko
AU - Kishimoto, Hiroyuki
AU - Kawai, Takashi
AU - Umeda, Yuzo
AU - Mishima, Hideyuki
AU - Goel, Ajay
AU - Fujiwara, Toshiyoshi
N1 - Funding Information:
The authors would like to thank Mr. Toru Nakai, Ms. Tae Yamanishi and Mr. Akihiro Nyuya for technical assistance. The authors would also like to thank Dr. Margaret Hinshelwood, of the Office of Scientific Publications at the Baylor Charles A. Sammons Cancer Center at Dallas for her helpful editorial comments. The present study was supported by KAKENHI (grant nos. 20590572, 25860409, 26462016 and 15H03034).
PY - 2018/2
Y1 - 2018/2
N2 - In stage IV colorectal cancer (CRC), initial resection of the primary tumor is considered to be an important strategy for improving disease outcome. However, there is no consensus on the timing as to when the surgical intervention of the primary tumor should occur. The present study hypothesizes that genetic profiles in CRC may indicate the appropriate treatment strategies for patients with stage IV CRC, and a cohort of 113 patients with stage IV CRC resected primary lesions at various periods were analyzed for the presence of mutations in the KRAS, exon 2, and BRAF genes, exon 15, and for the microsatellite instability status of the tumor. These data were additionally correlated with various clinicopathological features. Although BRAF-mutant was revealed to be an independent negative prognostic factor in stage IV CRC (HR, 8.42; 95% confidence interval, 2.72-26.02), BRAF-mutant samples exhibited better prognoses if they were treated with chemotherapy prior to tumor resection. Thus, the presence of BRAF mutations provides a compelling rationale for the establishment of intensive upfront chemotherapy to improve survival in stage IV CRC.
AB - In stage IV colorectal cancer (CRC), initial resection of the primary tumor is considered to be an important strategy for improving disease outcome. However, there is no consensus on the timing as to when the surgical intervention of the primary tumor should occur. The present study hypothesizes that genetic profiles in CRC may indicate the appropriate treatment strategies for patients with stage IV CRC, and a cohort of 113 patients with stage IV CRC resected primary lesions at various periods were analyzed for the presence of mutations in the KRAS, exon 2, and BRAF genes, exon 15, and for the microsatellite instability status of the tumor. These data were additionally correlated with various clinicopathological features. Although BRAF-mutant was revealed to be an independent negative prognostic factor in stage IV CRC (HR, 8.42; 95% confidence interval, 2.72-26.02), BRAF-mutant samples exhibited better prognoses if they were treated with chemotherapy prior to tumor resection. Thus, the presence of BRAF mutations provides a compelling rationale for the establishment of intensive upfront chemotherapy to improve survival in stage IV CRC.
KW - BRAF mutation
KW - Colorectal cancer
KW - KRAS mutation
KW - Microsatellite instability
KW - Stage IV
KW - Upfront chemotherapy
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U2 - 10.3892/ol.2017.7553
DO - 10.3892/ol.2017.7553
M3 - Article
AN - SCOPUS:85038447171
VL - 15
SP - 2195
EP - 2201
JO - Oncology Letters
JF - Oncology Letters
SN - 1792-1074
IS - 2
ER -