Prognostic relevance of KRAS and BRAF mutations in Japanese patients with colorectal cancer

Ryota Nakanishi, Jun Harada, Munkhbold Tuul, Yan Zhao, Koji Ando, Hiroshi Saeki, Eiji Oki, Takefumi Ohga, Hiroyuki Kitao, Yoshihiro Kakeji, Yoshihiko Maehara

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Background: Mutations of the KRAS or BRAF genes are now recognized as prognostic markers for colorectal cancer (CRC). They are also important predictive markers for resistance to the monoclonal antibodies that target the epidermal growth factor receptor. Methods: In this retrospective study, KRAS and BRAF mutations were analyzed using a direct sequence method in 254 Japanese CRC patients, and the associations between KRAS or BRAF mutations and clinicopathological characteristics or outcome were evaluated. Results: KRAS and BRAF mutations were detected in 33.5 and 6.7 % of all patients, respectively. Consistent with previous reports, BRAF mutations were significantly correlated with the anatomical site of the tumor (P < 0.001), tumor grade (P = 0.001) and high frequency of microsatellite instability (P < 0.001). BRAF mutations were correlated with poor overall survival in the full patient cohort (P = 0.009). KRAS mutations were significantly correlated with poor recurrence-free survival (P = 0.03), particularly in patients with stage II CRC (P = 0.007). Cox regression analysis showed that KRAS mutations were a negative predictor of recurrence-free survival in patients with stage II CRC. Conclusion: KRAS mutation status could be a novel biomarker for predicting disease recurrence in Japanese patients with stage II CRC.

Original languageEnglish
Pages (from-to)1042-1048
Number of pages7
JournalInternational Journal of Clinical Oncology
Volume18
Issue number6
DOIs
Publication statusPublished - Dec 1 2013

Fingerprint

Colorectal Neoplasms
Mutation
Recurrence
Survival
Microsatellite Instability
Epidermal Growth Factor Receptor
Neoplasms
Retrospective Studies
Biomarkers
Monoclonal Antibodies
Regression Analysis
Genes

All Science Journal Classification (ASJC) codes

  • Surgery
  • Hematology
  • Oncology

Cite this

Prognostic relevance of KRAS and BRAF mutations in Japanese patients with colorectal cancer. / Nakanishi, Ryota; Harada, Jun; Tuul, Munkhbold; Zhao, Yan; Ando, Koji; Saeki, Hiroshi; Oki, Eiji; Ohga, Takefumi; Kitao, Hiroyuki; Kakeji, Yoshihiro; Maehara, Yoshihiko.

In: International Journal of Clinical Oncology, Vol. 18, No. 6, 01.12.2013, p. 1042-1048.

Research output: Contribution to journalArticle

Nakanishi, Ryota ; Harada, Jun ; Tuul, Munkhbold ; Zhao, Yan ; Ando, Koji ; Saeki, Hiroshi ; Oki, Eiji ; Ohga, Takefumi ; Kitao, Hiroyuki ; Kakeji, Yoshihiro ; Maehara, Yoshihiko. / Prognostic relevance of KRAS and BRAF mutations in Japanese patients with colorectal cancer. In: International Journal of Clinical Oncology. 2013 ; Vol. 18, No. 6. pp. 1042-1048.
@article{b0bc3905f78c4c8b90fb089c99a9dd0f,
title = "Prognostic relevance of KRAS and BRAF mutations in Japanese patients with colorectal cancer",
abstract = "Background: Mutations of the KRAS or BRAF genes are now recognized as prognostic markers for colorectal cancer (CRC). They are also important predictive markers for resistance to the monoclonal antibodies that target the epidermal growth factor receptor. Methods: In this retrospective study, KRAS and BRAF mutations were analyzed using a direct sequence method in 254 Japanese CRC patients, and the associations between KRAS or BRAF mutations and clinicopathological characteristics or outcome were evaluated. Results: KRAS and BRAF mutations were detected in 33.5 and 6.7 {\%} of all patients, respectively. Consistent with previous reports, BRAF mutations were significantly correlated with the anatomical site of the tumor (P < 0.001), tumor grade (P = 0.001) and high frequency of microsatellite instability (P < 0.001). BRAF mutations were correlated with poor overall survival in the full patient cohort (P = 0.009). KRAS mutations were significantly correlated with poor recurrence-free survival (P = 0.03), particularly in patients with stage II CRC (P = 0.007). Cox regression analysis showed that KRAS mutations were a negative predictor of recurrence-free survival in patients with stage II CRC. Conclusion: KRAS mutation status could be a novel biomarker for predicting disease recurrence in Japanese patients with stage II CRC.",
author = "Ryota Nakanishi and Jun Harada and Munkhbold Tuul and Yan Zhao and Koji Ando and Hiroshi Saeki and Eiji Oki and Takefumi Ohga and Hiroyuki Kitao and Yoshihiro Kakeji and Yoshihiko Maehara",
year = "2013",
month = "12",
day = "1",
doi = "10.1007/s10147-012-0501-x",
language = "English",
volume = "18",
pages = "1042--1048",
journal = "International Journal of Clinical Oncology",
issn = "1341-9625",
publisher = "Springer Japan",
number = "6",

}

TY - JOUR

T1 - Prognostic relevance of KRAS and BRAF mutations in Japanese patients with colorectal cancer

AU - Nakanishi, Ryota

AU - Harada, Jun

AU - Tuul, Munkhbold

AU - Zhao, Yan

AU - Ando, Koji

AU - Saeki, Hiroshi

AU - Oki, Eiji

AU - Ohga, Takefumi

AU - Kitao, Hiroyuki

AU - Kakeji, Yoshihiro

AU - Maehara, Yoshihiko

PY - 2013/12/1

Y1 - 2013/12/1

N2 - Background: Mutations of the KRAS or BRAF genes are now recognized as prognostic markers for colorectal cancer (CRC). They are also important predictive markers for resistance to the monoclonal antibodies that target the epidermal growth factor receptor. Methods: In this retrospective study, KRAS and BRAF mutations were analyzed using a direct sequence method in 254 Japanese CRC patients, and the associations between KRAS or BRAF mutations and clinicopathological characteristics or outcome were evaluated. Results: KRAS and BRAF mutations were detected in 33.5 and 6.7 % of all patients, respectively. Consistent with previous reports, BRAF mutations were significantly correlated with the anatomical site of the tumor (P < 0.001), tumor grade (P = 0.001) and high frequency of microsatellite instability (P < 0.001). BRAF mutations were correlated with poor overall survival in the full patient cohort (P = 0.009). KRAS mutations were significantly correlated with poor recurrence-free survival (P = 0.03), particularly in patients with stage II CRC (P = 0.007). Cox regression analysis showed that KRAS mutations were a negative predictor of recurrence-free survival in patients with stage II CRC. Conclusion: KRAS mutation status could be a novel biomarker for predicting disease recurrence in Japanese patients with stage II CRC.

AB - Background: Mutations of the KRAS or BRAF genes are now recognized as prognostic markers for colorectal cancer (CRC). They are also important predictive markers for resistance to the monoclonal antibodies that target the epidermal growth factor receptor. Methods: In this retrospective study, KRAS and BRAF mutations were analyzed using a direct sequence method in 254 Japanese CRC patients, and the associations between KRAS or BRAF mutations and clinicopathological characteristics or outcome were evaluated. Results: KRAS and BRAF mutations were detected in 33.5 and 6.7 % of all patients, respectively. Consistent with previous reports, BRAF mutations were significantly correlated with the anatomical site of the tumor (P < 0.001), tumor grade (P = 0.001) and high frequency of microsatellite instability (P < 0.001). BRAF mutations were correlated with poor overall survival in the full patient cohort (P = 0.009). KRAS mutations were significantly correlated with poor recurrence-free survival (P = 0.03), particularly in patients with stage II CRC (P = 0.007). Cox regression analysis showed that KRAS mutations were a negative predictor of recurrence-free survival in patients with stage II CRC. Conclusion: KRAS mutation status could be a novel biomarker for predicting disease recurrence in Japanese patients with stage II CRC.

UR - http://www.scopus.com/inward/record.url?scp=84891489355&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84891489355&partnerID=8YFLogxK

U2 - 10.1007/s10147-012-0501-x

DO - 10.1007/s10147-012-0501-x

M3 - Article

C2 - 23188063

AN - SCOPUS:84891489355

VL - 18

SP - 1042

EP - 1048

JO - International Journal of Clinical Oncology

JF - International Journal of Clinical Oncology

SN - 1341-9625

IS - 6

ER -