Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 14, 2016; 22(30): 6764-6775
Published online Aug 14, 2016. doi: 10.3748/wjg.v22.i30.6764
Systematic review of the old and new concepts in the epithelial-mesenchymal transition of colorectal cancer
Simona Gurzu, Camelia Silveanu, Annamaria Fetyko, Vlad Butiurca, Zsolt Kovacs, Ioan Jung
Simona Gurzu, Camelia Silveanu, Annamaria Fetyko, Ioan Jung, Department of Pathology, University of Medicine and Pharmacy of Tirgu-Mures, 540139 Tirgu Mures, Romania
Vlad Butiurca, Department of Surgery, University of Medicine and Pharmacy of Tirgu-Mures, 540139 Tirgu Mures, Romania
Zsolt Kovacs, Departments of Genetics and Biochemistry, University of Medicine and Pharmacy of Tirgu-Mures, 540139 Tirgu Mures, Romania
Author contributions: Gurzu S designed research and drafted the article; Siveanu C collected the clinical data from histopathological reports; Fetyko A analyzed the immunohistochemical aspect of the daily cases and checked the English quality; Butiurca V analyzed the general data about epithelial-mesenchymal transition; Kovacs Z analyzed literature data in the field of prognostic role of epithelial-mesenchymal transition in colorectal cancer; Jung I designed research, blinded review the assessed records, and approved the final variant.
Supported by University of Medicine and Pharmacy of Tirgu-Mures, Romania, Team Research Projects Frame: UMFTGM-PO-CC-02-F01, No. 19/2014.
Conflict-of-interest statement: The authors have no conflict of interest to report.
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: Dr. Simona Gurzu, Professor, MD, PhD, Head of Department of Pathology, Research Center, University of Medicine and Pharmacy, 38 Ghe Marinescu Street, 540139 Tirgu Mures, Romania.
Telephone: +40-745673550 Fax: +40-265210407
Received: March 28, 2016
Peer-review started: April 3, 2016
First decision: May 12, 2016
Revised: June 3, 2016
Accepted: June 28, 2016
Article in press: June 28, 2016
Published online: August 14, 2016

Epithelial-to-mesenchymal transition (EMT) is defined as the transformation of an epithelial cell into a spindle cell with the loss of membrane E-cadherin expression and the gain of mesenchymal markers positivity. In the field of colorectal cancer (CRC), first data about EMT was published in 1995 and more than 400 papers had been written up to March 2016. Most of them are focused on the molecular pathways and experimentally-proved chemoresistance. In the present article, an update in the field of EMT in CRC based on the review of the literature and personal experience of the authors is presented. The information about the molecular and immunohistochemical (IHC) particularities of these processes and their possible role in the prognosis of CRC were also up-dated. This article focuses on the IHC quantification of the EMT, the immunoprofile of tumor buds and on the relation between EMT, angiogenesis, and stem cells activation. The EMT-induced chemoresistance vs chemotherapy- or radiotherapy-induced EMT and cellular senescence was also synthesized for both conventional and targeted therapy. As a future perspective, the EMT-angiogenesis-stemness link could be used as a possible valuable parameter for clinical follow-up and targeted therapeutic oncologic management of patients with CRC. Association of dexamethasone and angiotensin converting enzyme inhibitors combined with conventional chemotherapies could have clinical benefits in patients with CRC. The main conclusion is that, although many studies have been published, the EMT features are still incompletely elucidated and newly discovered EMT markers provide confusing data in understanding this complicated process, which might have significant clinical impact.

Keywords: Angiogenesis, Colorectal cancer, Budding, Epithelial-mesenchymal transition, Chemoresistance

Core tip: This review, based on the personal experience of gastrointestinal pathologists, is correlated with literature data and intended to provide an update in the field of epithelial-mesenchymal transition (EMT) in colorectal cancer. The link between EMT, tumor budding quantification, angiogenesis, renin-angiotensin system, and possible therapeutical impact is presented in detail.