Retrospective Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jan 15, 2016; 8(1): 128-135
Published online Jan 15, 2016. doi: 10.4251/wjgo.v8.i1.128
Impact of RAS and BRAF mutations on carcinoembryonic antigen production and pattern of colorectal metastases
May Cho, Chie Akiba, Cecilia Lau, David Smith, Milhan Telatar, Michelle Afkhami, Stephen Sentovich, Kurt Melstrom, Marwan Fakih
May Cho, Chie Akiba, Cecilia Lau, Marwan Fakih, Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA 91010, United States
David Smith, Department of Statistics, City of Hope National Medical Center, Duarte, CA 91010, United States
Milhan Telatar, Michelle Afkhami, Department of Pathology, City of Hope National Medical Center, Duarte, CA 91010, United States
Stephen Sentovich, Kurt Melstrom, Department of Surgical Oncology, City of Hope National Medical Center, Duarte, CA 91010, United States
Author contributions: Fakih M designed and supervised the trial; Fakih M and Cho M wrote the paper; Telatar M, Afkhami M, Sentovich S and Melstrom K contributed to the analysis; Cho M, Akiba C and Lau C collected and analysed data; Smith D did the statistical analysis.
Institutional review board statement: This study was reviewed and approved by the City of Hope National Medical Center.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data.
Conflict-of-interest statement: We have no pertinent financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Marwan Fakih, MD, Professor, Department of Medical Oncology, City of Hope National Medical Center, Building 51, Room 101, 1500 E Duarte St., Duarte, CA 91010, United States. mfakih@coh.org
Telephone: +1-626-2564673-63087 Fax: +1-626-3018233
Received: July 3, 2015
Peer-review started: July 10, 2015
First decision: September 30, 2015
Revised: October 22, 2015
Accepted: November 23, 2015
Article in press: November 25, 2015
Published online: January 15, 2016
Processing time: 195 Days and 11.2 Hours
Abstract

AIM: To investigate the impact of RAS and BRAF mutations on the pattern of metastatic disease and carcinoembryonic antigen (CEA) production.

METHODS: In this retrospective study, we investigated the impact of RAS and BRAF mutational status on pattern of metastatic disease and CEA production. Only patients presenting with a newly diagnosed metastatic colorectal cancer (CRC) were included. Patients’ characteristics, primary tumor location, site of metastatic disease and CEA at presentation were compared between those with and without RAS and BRAF mutations.

RESULTS: Among 174 patients, mutations in KRAS, NRAS and BRAF were detected in 47%, 3% and 6% respectively. RAS mutations (KRAS and NRAS) were more likely to be found in African American patients (87% vs 13%; P value = 0.0158). RAS mutations were associated with a higher likelihood of a normal CEA (< 5 ng/mL) at presentation. BRAF mutations were more likely to occur in females. We were not able to confirm any association between mutational status and site of metastatic disease at initial diagnosis.

CONCLUSION: No association was found between RAS and BRAF mutations and sites of metastatic disease at the time of initial diagnosis in our cohort. Patients with RAS mutations were more likely to present with CEA levels < 5 ng/mL. These findings may have clinical implications on surveillance strategies for RAS mutant patients with earlier stages of CRC.

Keywords: RAS; BRAF; Carcinoembryonic antigen; Pattern of metastatic disease; Surveillance

Core tip: We investigated the impact of RAS and BRAF mutations on pattern of colorectal cancer (CRC) metastases and carcinoembryonic antigen (CEA) production. Patients with RAS mutations were more likely to present with CEA levels < 5 ng/mL. No association was found between RAS and BRAF mutations and sites of metastatic disease at the time of initial diagnosis in our cohort. Our study is the first study to link low CEA production with a RAS mutant status at the time of initial presentation of metastatic CRC. These findings may have clinical implications on surveillance strategies for RAS mutant patients with earlier stages of CRC.