title: Sporadic colorectal cancer: Studying ways to an end.
abstract: BACKGROUND
  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.
  
  
  METHODS
  In a single-center, 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 BRAF and/or APC mutations. Macroscopically normal mucosa samples were tested for APC mutations. Presence and location of synchronous and metachronous adenomas and patient follow-up were analyzed. The association of two categorical variables was tested through the Fisher's exact test (SPSS 19).
  
  
  RESULTS
  Twenty-four patients (12 male, mean age 69 years) were studied. High-grade MSI (MSI-H) was found in eight tumors-these were significantly more common in the right colon (p = 0.047) and more likely to have an altered DRPE (p = 0.007). BRAF mutation was found in two of six tested MSI-H tumors. APC gene mutations were found in nine of 16 non-MSI-H tumors and absent in normal mucosa samples. There was a nonsignificant co-localization of CRC and synchronous adenomas and a significant co-localization (p = 0.05) of synchronous and metachronous adenomas.
  
  
  CONCLUSIONS
  Sporadic CRCs evolve through distinct pathways, evidenced only by pathological and molecular analysis, but clinically relevant both for patients and their families. In non-MSI-H tumors, the expected APC 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.
authors.affiliation: Serviço de Gastrenterologia do Instituto Português de Oncologia de Lisboa, Francisco Gentil (IPOLFG), EPE, Lisboa, Portugal; Faculdade de Ciências da Saúde da Universidade da Beira Interior, Covilhã, Portugal.
authors.forename: Isadora
authors.initials: I
authors.lastname: Rosa
authors.affiliation: Serviço de Gastrenterologia, Fundação Champalimaud, Lisboa, Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Fidalgo
authors.affiliation: Unidade de Investigação em Patobiologia Molecular, IPOLFG, EPE, Lisboa, Portugal.
authors.forename: Bruno
authors.initials: B
authors.lastname: Filipe
authors.affiliation: Unidade de Investigação em Patobiologia Molecular, IPOLFG, EPE, Lisboa, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Albuquerque
authors.affiliation: Serviço de Anatomia Patológica do IPOLFG, EPE, Lisboa, Portugal.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fonseca
authors.affiliation: Serviço de Anatomia Patológica do IPOLFG, EPE, Lisboa, Portugal; Faculdade de Ciências da Saúde da Universidade da Beira Interior, Covilhã, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Chaves
authors.affiliation: Serviço de Gastrenterologia do Instituto Português de Oncologia de Lisboa, Francisco Gentil (IPOLFG), EPE, Lisboa, Portugal; Faculdade de Ciências da Saúde da Universidade da Beira Interior, Covilhã, Portugal.
authors.forename: António D
authors.initials: AD
authors.lastname: Pereira
keywords: APC; Colorectal; cancer; field defect; pathways