{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T20:20:15Z","timestamp":1788726015861,"version":"build-2803163510"},"reference-count":90,"publisher":"Harborside Press, LLC","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> This study sought to assess microsatellite and <jats:italic>KRAS<\/jats:italic> status, prevalence, and impact on outcome in stage IV colorectal cancer (CRC). <jats:bold>Materials and Methods:<\/jats:bold> The 2010 to 2016 US National Cancer Database was queried for adult patients with stage IV CRC. Prevalence of microsatellite status (microsatellite instability\u2013high [MSI-H] or microsatellite stable [MSS]) and <jats:italic>KRAS<\/jats:italic> status (<jats:italic>KRAS<\/jats:italic> 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 <jats:italic>KRAS<\/jats:italic> status and information on follow-up. <jats:bold>Results:<\/jats:bold> Information on microsatellite and <jats:italic>KRAS<\/jats:italic> 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 <jats:italic>KRAS<\/jats:italic> 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 <jats:italic>KRAS<\/jats:italic> mutation. MSI-H rates were highest in East North Central US states (4.1%), and <jats:italic>KRAS<\/jats:italic> mutation rates were highest in West South Central US states (44.1%). Multivariable analyses revealed longer OS for patients with <jats:italic>KRAS<\/jats:italic> wild-type versus mutation status (hazard ratio [HR], 0.91; 95% CI, 0.85\u20130.97; <jats:italic>P=<\/jats:italic>.004), those with MSS versus MSI-H status (HR, 0.75; 95% CI, 0.62\u20130.9; <jats:italic>P=<\/jats:italic>.003), and those with left-sided versus right-sided CRC (multivariable HR, 0.65; 95% CI, 0.6\u20130.7; <jats:italic>P&lt;<\/jats:italic>.001). The effect of <jats:italic>KRAS<\/jats:italic> mutation further varied with CRC site and microsatellite status (<jats:italic>P=<\/jats:italic>.002 for interaction). <jats:bold>Conclusions:<\/jats:bold> Depending on the primary site and US geography, stage IV CRC shows distinct mutational behavior. <jats:italic>KRAS<\/jats:italic> 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.<\/jats:p>","DOI":"10.6004\/jnccn.2020.7619","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T21:35:51Z","timestamp":1614980151000},"page":"307-318","source":"Crossref","is-referenced-by-count":27,"title":["Microsatellite Instability and KRAS Mutation in Stage IV Colorectal Cancer: Prevalence, Geographic Discrepancies, and Outcomes From the National Cancer Database"],"prefix":"10.6004","volume":"19","author":[{"given":"Johannes","family":"Uhlig","sequence":"first","affiliation":[{"name":"1Section of Interventional Radiology, Yale School of Medicine, New Haven, Connecticut;"},{"name":"2Department of Diagnostic and Interventional Radiology, University Medical Center Goettingen, Goettingen, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Cecchini","sequence":"additional","affiliation":[{"name":"3Section of Medical Oncology, Yale School of Medicine, and"},{"name":"4Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amar","family":"Sheth","sequence":"additional","affiliation":[{"name":"1Section of Interventional Radiology, Yale School of Medicine, New Haven, Connecticut;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey","family":"Stein","sequence":"additional","affiliation":[{"name":"3Section of Medical Oncology, Yale School of Medicine, and"},{"name":"4Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Lacy","sequence":"additional","affiliation":[{"name":"3Section of Medical Oncology, Yale School of Medicine, and"},{"name":"4Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun S.","family":"Kim","sequence":"additional","affiliation":[{"name":"1Section of Interventional Radiology, Yale School of Medicine, New Haven, Connecticut;"},{"name":"3Section of Medical Oncology, Yale School of Medicine, and"},{"name":"4Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4047","reference":[{"key":"ref491","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1158\/1078-0432.CCR-13-1573","article-title":"NSAIDs inhibit tumorigenesis, but how?","volume":"20","author":"Gurpinar","year":"2014","journal-title":"Clin Cancer Res"},{"key":"ref461","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1093\/annonc\/mdu100","article-title":"Multicenter retrospective analysis of metastatic colorectal cancer (CRC) with high-level microsatellite instability (MSI-H)","volume":"25","author":"Goldstein","year":"2014","journal-title":"Ann 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