Prospective Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 28, 2016; 22(20): 4936-4945
Published online May 28, 2016. doi: 10.3748/wjg.v22.i20.4936
Longitudinal molecular characterization of endoscopic specimens from colorectal lesions
Petra Minarikova, Lucie Benesova, Tereza Halkova, Barbora Belsanova, Stepan Suchanek, Jiri Cyrany, Inna Tuckova, Jan Bures, Miroslav Zavoral, Marek Minarik
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
Lucie Benesova, Tereza Halkova, Barbora Belsanova, Marek Minarik, Genomac Research Institute, Centre for Applied Genomics of Solid Tumors, CZ 16100 Prague, Czech Republic
Jiri Cyrany, Jan Bures, 2nd Department of Internal Medicine - Gastroenterology, Charles University, Faculty of Medicine at Hradec Kralove, University Teaching Hospital, CZ 50005 Hradec Kralove, Czech Republic
Author contributions: Minarikova P, Benesova L and Minarik M designed the study; Halkova T, Belsanova B and Cyrany J performed the research; Benesova L, Halkova T and Suchanek S analyzed the data; Minarikova P, Benesova L and Minarik M wrote the paper; Bures J and Zavoral M revised the manuscript for final submission.
Supported by Internal Grant Agency of the Czech Ministry of Health, No. NT 14383.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of the Military University Hospital, Prague.
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All authors declare no conflict of interest.
Data sharing statement: Technical and clinical data is available from the corresponding author at Participants have consented to use of their data for further research and other non-commercial purposes.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Marek Minarik, PhD, Director, Genomac Research Institute, Centre for Applied Genomics of Solid Tumors, CZ 16100 Prague, Czech Republic.
Telephone: +420-226203530 Fax: +420-226203542
Received: February 24, 2016
Peer-review started: February 29, 2016
First decision: March 21, 2016
Revised: April 9, 2016
Accepted: May 4, 2016
Article in press: May 4, 2016
Published online: May 28, 2016

AIM: 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.

CONCLUSION: 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.

Keywords: Colorectal cancer, CpG-island methylator phenotype, DNA, Microsatellite instability, BRAF

Core tip: The results indicate that molecular subtyping from endoscopic biopsies is feasible in routine gastroenterology practice to evaluate a patient’s prognosis. Subtyping based on Jass classification can be used to evaluate molecular mechanisms of adenoma-carcinoma transition.