Poor prognosis of KRAS or BRAF mutant colorectal liver metastasis without microsatellite instability

Yuzo Umeda, Takeshi Nagasaka, Yoshiko Mori, Hiroshi Sadamori, Dong Sheng Sun, Susumu Shinoura, Ryuichi Yoshida, Daisuke Satoh, Daisuke Nobuoka, Masashi Utsumi, Kazuhiro Yoshida, Takahito Yagi, Toshiyoshi Fujiwara

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background: The discovery of practical biomarkers is important to realize personalized medicine for patients with malignant neoplasias, including colorectal cancer (CRC). Purpose: The aim of this study was to determine reliable prognostic biomarkers by the analysis of patients with resectable colorectal liver metastases (CRLM). Methods: Genomic DNA was obtained from the CRLM tissues of a cohort of 126 patients with CRLM with curative hepatic resection. The KRAS/BRAF mutation spectrum and microsatellite instability (MSI) status were successfully analyzed in 100 of the 126 CRLM tissues and these findings were examined in relation to the patients' clinical outcomes. Results: The cohort of 100 CRLM patients consisted of 46 with synchronous and 54 with metachronous liver metastasis. Overall survival and disease-free survival at 5 years were 57.4 and 24.9 %, respectively. MSI analysis revealed that none of the 100 CRLM specimens showed any evidence of MSI. By KRAS/BRAF mutation analysis, the analyzed CRLM patients were divided into 3 groups; KRAS-mutant (KRAS-Mt; n = 27), BRAF-mutant (BRAF-Mt; n = 3), and wild-types of both genes (Wild-type; n = 70). In the survival analysis, both KRAS-Mt and BRAF-Mt patients showed significantly poorer prognoses compared with Wild-type patients. Furthermore, although the population with the BRAF mutation was small, this mutation had a significant negative impact on disease-free survival. Conclusions: In this study, all tumors in the cohort of CRLM patients were non-MSI tumors, suggesting MSI cancer in primary CRC would rarely reveal metastatic potential. KRAS and BRAF mutations are suggested to be poor prognostic factors in CRLM. Genetic information has an essential role as a prognostic marker and could contribute to the decisions on treatment strategy for CRLM.

Original languageEnglish
Pages (from-to)223-233
Number of pages11
JournalJournal of Hepato-Biliary-Pancreatic Sciences
Volume20
Issue number2
DOIs
Publication statusPublished - Feb 2013

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Microsatellite Instability
Neoplasm Metastasis
Liver
Mutation
Disease-Free Survival
Colorectal Neoplasms
Neoplasms
Biomarkers
Precision Medicine
Survival Analysis

Keywords

  • BRAF
  • Colorectal cancer
  • KRAS
  • Liver metastasis
  • Microsatellite instability

ASJC Scopus subject areas

  • Hepatology
  • Surgery

Cite this

Poor prognosis of KRAS or BRAF mutant colorectal liver metastasis without microsatellite instability. / Umeda, Yuzo; Nagasaka, Takeshi; Mori, Yoshiko; Sadamori, Hiroshi; Sun, Dong Sheng; Shinoura, Susumu; Yoshida, Ryuichi; Satoh, Daisuke; Nobuoka, Daisuke; Utsumi, Masashi; Yoshida, Kazuhiro; Yagi, Takahito; Fujiwara, Toshiyoshi.

In: Journal of Hepato-Biliary-Pancreatic Sciences, Vol. 20, No. 2, 02.2013, p. 223-233.

Research output: Contribution to journalArticle

Umeda, Yuzo ; Nagasaka, Takeshi ; Mori, Yoshiko ; Sadamori, Hiroshi ; Sun, Dong Sheng ; Shinoura, Susumu ; Yoshida, Ryuichi ; Satoh, Daisuke ; Nobuoka, Daisuke ; Utsumi, Masashi ; Yoshida, Kazuhiro ; Yagi, Takahito ; Fujiwara, Toshiyoshi. / Poor prognosis of KRAS or BRAF mutant colorectal liver metastasis without microsatellite instability. In: Journal of Hepato-Biliary-Pancreatic Sciences. 2013 ; Vol. 20, No. 2. pp. 223-233.
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abstract = "Background: The discovery of practical biomarkers is important to realize personalized medicine for patients with malignant neoplasias, including colorectal cancer (CRC). Purpose: The aim of this study was to determine reliable prognostic biomarkers by the analysis of patients with resectable colorectal liver metastases (CRLM). Methods: Genomic DNA was obtained from the CRLM tissues of a cohort of 126 patients with CRLM with curative hepatic resection. The KRAS/BRAF mutation spectrum and microsatellite instability (MSI) status were successfully analyzed in 100 of the 126 CRLM tissues and these findings were examined in relation to the patients' clinical outcomes. Results: The cohort of 100 CRLM patients consisted of 46 with synchronous and 54 with metachronous liver metastasis. Overall survival and disease-free survival at 5 years were 57.4 and 24.9 {\%}, respectively. MSI analysis revealed that none of the 100 CRLM specimens showed any evidence of MSI. By KRAS/BRAF mutation analysis, the analyzed CRLM patients were divided into 3 groups; KRAS-mutant (KRAS-Mt; n = 27), BRAF-mutant (BRAF-Mt; n = 3), and wild-types of both genes (Wild-type; n = 70). In the survival analysis, both KRAS-Mt and BRAF-Mt patients showed significantly poorer prognoses compared with Wild-type patients. Furthermore, although the population with the BRAF mutation was small, this mutation had a significant negative impact on disease-free survival. Conclusions: In this study, all tumors in the cohort of CRLM patients were non-MSI tumors, suggesting MSI cancer in primary CRC would rarely reveal metastatic potential. KRAS and BRAF mutations are suggested to be poor prognostic factors in CRLM. Genetic information has an essential role as a prognostic marker and could contribute to the decisions on treatment strategy for CRLM.",
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T1 - Poor prognosis of KRAS or BRAF mutant colorectal liver metastasis without microsatellite instability

AU - Umeda, Yuzo

AU - Nagasaka, Takeshi

AU - Mori, Yoshiko

AU - Sadamori, Hiroshi

AU - Sun, Dong Sheng

AU - Shinoura, Susumu

AU - Yoshida, Ryuichi

AU - Satoh, Daisuke

AU - Nobuoka, Daisuke

AU - Utsumi, Masashi

AU - Yoshida, Kazuhiro

AU - Yagi, Takahito

AU - Fujiwara, Toshiyoshi

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KW - Colorectal cancer

KW - KRAS

KW - Liver metastasis

KW - Microsatellite instability

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