{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T10:12:53Z","timestamp":1693822373115},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,4,1]],"date-time":"2016-04-01T00:00:00Z","timestamp":1459468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2016,4,1]],"date-time":"2016-04-01T00:00:00Z","timestamp":1459468800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100007054","name":"Meso Scale Diagnostics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["UEG Journal"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Although colorectal cancer (CRC) has often been regarded as a single entity, different pathways may lead to macroscopically similar cancers. These pathways may evolve into a patchy colonic field defect that we aimed to study in consecutive CRC patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a single\u2010center, observational, prospective study, consecutive CRC patients were included if surgery and a perioperative colonoscopy were planned. Personal and familial history data were collected. Tumors were studied for microsatellite instability (MSI) status, DNA repair protein expression (DRPE) and presence of <jats:italic>BRAF<\/jats:italic> and\/or <jats:italic>APC<\/jats:italic> mutations. Macroscopically normal mucosa samples were tested for <jats:italic>APC<\/jats:italic> mutations. Presence and location of synchronous and metachronous adenomas and patient follow\u2010up were analyzed. The association of two categorical variables was tested through the Fisher\u2019s exact test (SPSS 19).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010four patients (12\u00a0male, mean age 69 years) were studied. High\u2010grade MSI (MSI\u2010H) was found in eight tumors\u2014these were significantly more common in the right colon (<jats:italic>p<\/jats:italic> \u2009=\u20090.047) and more likely to have an altered DRPE (<jats:italic>p<\/jats:italic> \u2009=\u20090.007). <jats:italic>BRAF<\/jats:italic> mutation was found in two of six tested MSI\u2010H tumors. <jats:italic>APC<\/jats:italic> gene mutations were found in nine of 16\u00a0non\u2010MSI\u2010H tumors and absent in normal mucosa samples. There was a nonsignificant co\u2010localization of CRC and synchronous adenomas and a significant co\u2010localization (<jats:italic>p<\/jats:italic> \u2009=\u20090.05) of synchronous and metachronous adenomas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Sporadic CRCs evolve through distinct pathways, evidenced only by pathological and molecular analysis, but clinically relevant both for patients and their families. In non\u2010MSI\u2010H tumors, the expected <jats:italic>APC<\/jats:italic> gene mutations were not detected by the most commonly used techniques in a high number of cases. More studies are needed to fully characterize these tumors and to search for common early events in normal mucosa patches, which might explain the indirect evidence found here for a field defect in the colon.<\/jats:p><\/jats:sec>","DOI":"10.1177\/2050640615599329","type":"journal-article","created":{"date-parts":[[2015,8,7]],"date-time":"2015-08-07T02:39:20Z","timestamp":1438915160000},"page":"288-296","update-policy":"http:\/\/dx.doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Sporadic colorectal cancer: Studying ways to an end"],"prefix":"10.1002","volume":"4","author":[{"given":"Isadora","family":"Rosa","sequence":"first","affiliation":[{"name":"Servi\u00e7o de Gastrenterologia do Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil (IPOLFG) EPE Lisboa Portugal"},{"name":"Faculdade de Ci\u00eancias da Sa\u00fade da Universidade da Beira Interior Covilh\u00e3 Portugal"}]},{"given":"Paulo","family":"Fidalgo","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Gastrenterologia Funda\u00e7\u00e3o Champalimaud Lisboa Portugal"}]},{"given":"Bruno","family":"Filipe","sequence":"additional","affiliation":[{"name":"Unidade de Investiga\u00e7\u00e3o em Patobiologia Molecular IPOLFG EPE Lisboa Portugal"}]},{"given":"Cristina","family":"Albuquerque","sequence":"additional","affiliation":[{"name":"Unidade de Investiga\u00e7\u00e3o em Patobiologia Molecular IPOLFG EPE Lisboa Portugal"}]},{"given":"Ricardo","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Anatomia Patol\u00f3gica do IPOLFG EPE Lisboa Portugal"}]},{"given":"Paula","family":"Chaves","sequence":"additional","affiliation":[{"name":"Faculdade de Ci\u00eancias da Sa\u00fade da Universidade da Beira Interior Covilh\u00e3 Portugal"},{"name":"Servi\u00e7o de Anatomia Patol\u00f3gica do IPOLFG EPE Lisboa Portugal"}]},{"given":"Ant\u00f3nio D","family":"Pereira","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Gastrenterologia do Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil (IPOLFG) EPE Lisboa Portugal"},{"name":"Faculdade de Ci\u00eancias da Sa\u00fade da Universidade da Beira Interior Covilh\u00e3 Portugal"}]}],"member":"311","published-online":{"date-parts":[[2016,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.959840"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.222118199"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/1471-2407-5-126","article-title":"Numbers of mutations to different types of colorectal cancer","volume":"5","author":"Calabrese P","year":"2005","journal-title":"BMC Cancer"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mbs.2005.06.003"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra061808"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05372"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05384"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/422494a"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.03.002"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07602"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-003-2289-3"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1840"},{"key":"e_1_2_9_14_1","first-page":"1337","article-title":"Clonal evolution of human stem cell populations","volume":"16","author":"Calabrese P","year":"2004","journal-title":"Am J Pathol"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-10-3"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/embr.201337799"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1243148"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.05.007"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909343106"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11252"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2007.00766.x"},{"key":"e_1_2_9_22_1","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/S0016-5085(99)70510-X","article-title":"New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC","volume":"116","author":"Vassen HF","year":"1999","journal-title":"Gastroenterology"},{"key":"e_1_2_9_23_1","first-page":"135","volume-title":"World Health Organization classification of tumours. 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