Johannes Uhlig1,2, Michael Cecchini3,4, Amar Sheth1, Stacey Stein3,4, Jill Lacy3,4, Hyun S Kim1,3,4. 1. 1Section of Interventional Radiology, Yale School of Medicine, New Haven, Connecticut. 2. 2Department of Diagnostic and Interventional Radiology, University Medical Center Goettingen, Goettingen, Germany; and. 3. 3Section of Medical Oncology, Yale School of Medicine, and. 4. 4Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut.
Abstract
BACKGROUND: This study sought to assess microsatellite and KRAS status, prevalence, and impact on outcome in stage IV colorectal cancer (CRC). MATERIALS AND METHODS: The 2010 to 2016 US National Cancer Database was queried for adult patients with stage IV CRC. Prevalence of microsatellite status (microsatellite instability-high [MSI-H] or microsatellite stable [MSS]) and KRAS status (KRAS mutation or wild-type) of the primary CRC was assessed. Overall survival (OS) was evaluated using multivariable Cox proportional hazards models in patients with complete data on both microsatellite and KRAS status and information on follow-up. RESULTS: Information on microsatellite and KRAS status was available for 10,844 and 25,712 patients, respectively, and OS data were available for 5,904 patients. The overall prevalence of MSI-H status and KRAS mutation was 3.1% and 42.4%, respectively. Prevalence of MSI-H ranged between 1.6% (rectosigmoid junction) and 5.2% (transverse colon), and between 34.7% (sigmoid colon) and 58.2% (cecum) for KRAS mutation. MSI-H rates were highest in East North Central US states (4.1%), and KRAS mutation rates were highest in West South Central US states (44.1%). Multivariable analyses revealed longer OS for patients with KRAS wild-type versus mutation status (hazard ratio [HR], 0.91; 95% CI, 0.85-0.97; P=.004), those with MSS versus MSI-H status (HR, 0.75; 95% CI, 0.62-0.9; P=.003), and those with left-sided versus right-sided CRC (multivariable HR, 0.65; 95% CI, 0.6-0.7; P<.001). The effect of KRAS mutation further varied with CRC site and microsatellite status (P=.002 for interaction). CONCLUSIONS: Depending on the primary site and US geography, stage IV CRC shows distinct mutational behavior. KRAS mutation, MSI-H, and primary CRC sidedness independently affect OS and interact with distinct prognostic profiles. Generically classifying adenocarcinomas at different sites as CRC might deprecate this diversity.
BACKGROUND: This study sought to assess microsatellite and KRAS status, prevalence, and impact on outcome in stage IV colorectal cancer (CRC). MATERIALS AND METHODS: The 2010 to 2016 US National Cancer Database was queried for adult patients with stage IV CRC. Prevalence of microsatellite status (microsatellite instability-high [MSI-H] or microsatellite stable [MSS]) and KRAS status (KRAS mutation or wild-type) of the primary CRC was assessed. Overall survival (OS) was evaluated using multivariable Cox proportional hazards models in patients with complete data on both microsatellite and KRAS status and information on follow-up. RESULTS: Information on microsatellite and KRAS status was available for 10,844 and 25,712 patients, respectively, and OS data were available for 5,904 patients. The overall prevalence of MSI-H status and KRAS mutation was 3.1% and 42.4%, respectively. Prevalence of MSI-H ranged between 1.6% (rectosigmoid junction) and 5.2% (transverse colon), and between 34.7% (sigmoid colon) and 58.2% (cecum) for KRAS mutation. MSI-H rates were highest in East North Central US states (4.1%), and KRAS mutation rates were highest in West South Central US states (44.1%). Multivariable analyses revealed longer OS for patients with KRAS wild-type versus mutation status (hazard ratio [HR], 0.91; 95% CI, 0.85-0.97; P=.004), those with MSS versus MSI-H status (HR, 0.75; 95% CI, 0.62-0.9; P=.003), and those with left-sided versus right-sided CRC (multivariable HR, 0.65; 95% CI, 0.6-0.7; P<.001). The effect of KRAS mutation further varied with CRC site and microsatellite status (P=.002 for interaction). CONCLUSIONS: Depending on the primary site and US geography, stage IV CRC shows distinct mutational behavior. KRAS mutation, MSI-H, and primary CRC sidedness independently affect OS and interact with distinct prognostic profiles. Generically classifying adenocarcinomas at different sites as CRC might deprecate this diversity.
Authors: Yue-Ju Li; Cheng-Ning Yang; Mark Yen-Ping Kuo; Wei-Ting Lai; Tai-Sheng Wu; Been-Ren Lin Journal: Am J Cancer Res Date: 2022-08-15 Impact factor: 5.942
Authors: Hafeez Afolabi; Salzihan Md Salleh; Zaidi Zakaria; Ch'ng Ewe Seng; Siti Norasikin Binti Mohd Nafil; Ahmad Aizat Bin Abdul Aziz; Yusuf Wada; Ahmad Irekeola Journal: Biomed Res Int Date: 2022-06-23 Impact factor: 3.246