title: Biomarkers for the identification of precursor polyps of colorectal serrated adenocarcinomas.
abstract: BACKGROUND
  In contrast to conventional colorectal carcinomas (CCs), which develop through a so-called chromosome instability or suppressor phenotype pathway, the sequence of events leading from precursor polyps/adenomas to serrated adenocarcinomas (SACs), which are more aggressive and exhibit a poorer survival than CCs, is as yet not clearly defined. Here, we aimed at detecting protein and DNA biomarkers for SAC in a series of primary colorectal polyps.
  
  
  METHODS
  In total 303 colorectal polyps were included: 121 serrated polyps (33 hyperplastic polyps, 37 sessile serrated adenomas (SSA), 51 traditional serrated adenomas (TSA)), 143 conventional polyps (72 tubular polyps, 34 tubulovillous polyps, 37 villious adenomas), and 39 bi-phenotypic serrated-conventional polyps. The protein biomarkers tested were deduced from previously published SAC and CC expression profiling studies. A representative subset of 106 polyps was selected for DNA biomarker analyses, i.e., proto-oncogene mutation and microsatellite instability (MSI) status. In order to confer proper weight to each biomarker, a multivariate logistic regression model was employed.
  
  
  RESULTS
  We found that serrated and conventional polyps differed in most of the SAC biomarkers tested. Of these biomarkers, FSCN1 showed the largest difference in expression (p = 0.0001). Despite sharing a serrated morphology, we found that SSAs and TSAs differed considerably with respect to anatomical location, expression of EPHB2 and PTCH1, presence of the V600E BRAF mutation and MSI status. Logistic regression analysis revealed that SSA was the polyp type that shared most biomarkers with SAC.
  
  
  CONCLUSIONS
  Based on the shared presence of protein and molecular biomarkers, especially FSCN1 expression, SSA may serve as a precursor lesion of SAC. Biomarker assessment may help in discerning colorectal carcinogenic routes with distinct prognostic implications.
authors.affiliation: Department of Pathology, Santa Lucía General University Hospital (HGUSL), 30202, Cartagena, Spain.|Facultad de Ciencias de la Salud, Catholic University of Murcia (UCAM), 30107, Murcia, Spain.
authors.forename: José
authors.initials: J
authors.lastname: García-Solano
authors.affiliation: Department of Pathology, Santa Lucía General University Hospital (HGUSL), 30202, Cartagena, Spain.
authors.forename: María Eulalia
authors.initials: ME
authors.lastname: García-Solano
authors.affiliation: Department of Pathology, Santa Lucía General University Hospital (HGUSL), 30202, Cartagena, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Torres-Moreno
authors.affiliation: Biochemistry and Clinical Genetic Centre, Virgen Arrixaca University Hospital, 30120, Murcia, El Palmar, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Carbonell
authors.affiliation: Department of Internal Medicine, HGUSL, 30202, Cartagena, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Trujillo-Santos
authors.affiliation: Department of Pathology, Santa Lucía General University Hospital (HGUSL), 30202, Cartagena, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Pérez-Guillermo
authors.affiliation: Facultad de Ciencias de la Salud, Catholic University of Murcia (UCAM), 30107, Murcia, Spain. pablo.conesa@carm.es.|Department of Clinical Analysis, HGUSL, 30202, Cartagena, Spain. pablo.conesa@carm.es.
authors.forename: Pablo
authors.initials: P
authors.lastname: Conesa-Zamora
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000236:Adenoma / Q000235:genetics / Q000473:pathology*; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D003111:Colonic Polyps / Q000235:genetics / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology; D000090063:Proto-Oncogene Mas
chemical_list: D014408:Biomarkers, Tumor; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas
keywords: Biomarkers; Carcinogenesis; Colorectal cancer; Serrated adenocarcinoma; Serrated polyp
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