title: Longitudinal molecular characterization of endoscopic specimens from colorectal lesions.
abstract: OBJECTIVE
  To compare molecular profiles of proximal colon, distal colon and rectum in large adenomas, early and late carcinomas. To assess feasibility of testing directed at molecular markers from this study in routine clinical practice.
  
  
  METHODS
  A prospective 3-year study has resulted in the acquisition of samples from 159 large adenomas and 138 carcinomas along with associated clinical parameters including localization, grade and histological type for adenomas and localization and stage for carcinomas. A complex molecular phenotyping has been performed using multiplex ligation-dependent probe amplification technique for the evaluation of CpG-island methylator phenotype (CIMP), PCR fragment analysis for detection of microsatellite instability and denaturing capillary electrophoresis for sensitive detection of somatic mutations in KRAS, BRAF, TP53 and APC genes.
  
  
  RESULTS
  Molecular types according to previously introduced Jass classification have been evaluated for large adenomas and early and late carcinomas. An increase in CIMP+ type, eventually accompanied with KRAS mutations, was notable between large adenomas and early carcinomas. As expected, the longitudinal observations revealed a correlation of the CIMP+/BRAF+ type with proximal location.
  
  
  CONCLUSIONS
  Prospective molecular classification of tissue specimens is feasible in routine endoscopy practice. Increased frequency of some molecular types corresponds to the developmental stages of colorectal tumors. As expected, a clear distinction is notable for tumors located in proximal colon supposedly arising from the serrated (methylation) pathway.
authors.affiliation: Petra Minarikova, Stepan Suchanek, Miroslav Zavoral, Inna Tuckova, Marek Minarik, Department of Internal Medicine, 1st Faculty of Medicine of Charles University and Military University Hospital, CZ 16902 Prague, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Minarikova
authors.affiliation: Petra Minarikova, Stepan Suchanek, Miroslav Zavoral, Inna Tuckova, Marek Minarik, Department of Internal Medicine, 1st Faculty of Medicine of Charles University and Military University Hospital, CZ 16902 Prague, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Benesova
authors.affiliation: Petra Minarikova, Stepan Suchanek, Miroslav Zavoral, Inna Tuckova, Marek Minarik, Department of Internal Medicine, 1st Faculty of Medicine of Charles University and Military University Hospital, CZ 16902 Prague, Czech Republic.
authors.forename: Tereza
authors.initials: T
authors.lastname: Halkova
authors.affiliation: Petra Minarikova, Stepan Suchanek, Miroslav Zavoral, Inna Tuckova, Marek Minarik, Department of Internal Medicine, 1st Faculty of Medicine of Charles University and Military University Hospital, CZ 16902 Prague, Czech Republic.
authors.forename: Barbora
authors.initials: B
authors.lastname: Belsanova
authors.affiliation: Petra Minarikova, Stepan Suchanek, Miroslav Zavoral, Inna Tuckova, Marek Minarik, Department of Internal Medicine, 1st Faculty of Medicine of Charles University and Military University Hospital, CZ 16902 Prague, Czech Republic.
authors.forename: Stepan
authors.initials: S
authors.lastname: Suchanek
authors.affiliation: Petra Minarikova, Stepan Suchanek, Miroslav Zavoral, Inna Tuckova, Marek Minarik, Department of Internal Medicine, 1st Faculty of Medicine of Charles University and Military University Hospital, CZ 16902 Prague, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Cyrany
authors.affiliation: Petra Minarikova, Stepan Suchanek, Miroslav Zavoral, Inna Tuckova, Marek Minarik, Department of Internal Medicine, 1st Faculty of Medicine of Charles University and Military University Hospital, CZ 16902 Prague, Czech Republic.
authors.forename: Inna
authors.initials: I
authors.lastname: Tuckova
authors.affiliation: Petra Minarikova, Stepan Suchanek, Miroslav Zavoral, Inna Tuckova, Marek Minarik, Department of Internal Medicine, 1st Faculty of Medicine of Charles University and Military University Hospital, CZ 16902 Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Bures
authors.affiliation: Petra Minarikova, Stepan Suchanek, Miroslav Zavoral, Inna Tuckova, Marek Minarik, Department of Internal Medicine, 1st Faculty of Medicine of Charles University and Military University Hospital, CZ 16902 Prague, Czech Republic.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Zavoral
authors.affiliation: Petra Minarikova, Stepan Suchanek, Miroslav Zavoral, Inna Tuckova, Marek Minarik, Department of Internal Medicine, 1st Faculty of Medicine of Charles University and Military University Hospital, CZ 16902 Prague, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Minarik
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D018899:CpG Islands; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)
keywords: BRAF; Colorectal cancer; CpG-island methylator phenotype; DNA; Microsatellite instability