Kövecsi A, Gurzu S, Szentirmay Z, Kovacs Z, Bara TJ, Jung I. Paradoxical expression pattern of the epithelial mesenchymal transition-related biomarkers CD44, SLUG, N-cadherin and VSIG1/Glycoprotein A34 in gastrointestinal stromal tumors. World J Gastrointest Oncol 2017; 9(11): 436-443 [PMID: 29204252 DOI: 10.4251/wjgo.v9.i11.436]
Corresponding Author of This Article
Simona Gurzu, MD, PhD, Professor, Head of Department of Pathology, University of Medicine and Pharmacy, Gheorghe Marinescu 38 street, Tirgu Mures 540139, Romania. simona.gurzu@umftgm.ro
Research Domain of This Article
Oncology
Article-Type of This Article
Retrospective Cohort Study
Open-Access Policy of This Article
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: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. Nov 15, 2017; 9(11): 436-443 Published online Nov 15, 2017. doi: 10.4251/wjgo.v9.i11.436
Paradoxical expression pattern of the epithelial mesenchymal transition-related biomarkers CD44, SLUG, N-cadherin and VSIG1/Glycoprotein A34 in gastrointestinal stromal tumors
Attila Kövecsi, Simona Gurzu, Zoltan Szentirmay, Zsolt Kovacs, Tivadar Jr Bara, Ioan Jung
Attila Kövecsi, Simona Gurzu, Zsolt Kovacs, Ioan Jung, Department of Pathology, University of Medicine and Pharmacy, Tirgu Mures 540139, Romania
Simona Gurzu, Research Center, University of Medicine and Pharmacy, Timi oara 3000041, Romania
Zoltan Szentirmay, Department of Pathology, National Institute of Oncology, Budapest 1525, Hungary
Zsolt Kovacs, Department of Biochemistry, University of Medicine and Pharmacy, Timi oara 3000041, Romania
Tivadar Jr Bara, Department of Surgery, University of Medicine and Pharmacy, Timi oara 3000041, Romania
Author contributions: Kovecsi A drafted the article and contributed to interpretation of the immunostains; Gurzu S designed research and contributed to the diagnosis and statistical assessment; Szentirmay Z performed the molecular examinations; Kovacs Z contributed to the molecular examinations; Bara T Jr performed the surgical interventions; Bara T Jr participated at the surgical interventions and the clinical assessment of the cases; Jung I performed the interpretation of the immunohistochemical stains and confer the final agreement for publication; Kövecsi A and Bara T Jr have equal contribution to the paper.
Supported by University of Medicine and Pharmacy of Tirgu-Mures, Romania, in the joint project with Studium Prospero Foundation and Hungarian Science Academy, research projects frame 136/2017.
Conflict-of-interest statement: None declared.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Simona Gurzu, MD, PhD, Professor, Head of Department of Pathology, University of Medicine and Pharmacy, Gheorghe Marinescu 38 street, Tirgu Mures 540139, Romania. simona.gurzu@umftgm.ro
Telephone: +40-745-673550 Fax: +40-265-210407
Received: May 29, 2017 Peer-review started: June 6, 2017 First decision: July 26, 2017 Revised: July 31, 2017 Accepted: September 5, 2017 Article in press: September 6, 2017 Published online: November 15, 2017 Processing time: 168 Days and 11.9 Hours
Abstract
AIM
To evaluate the immunohistochemical (IHC) expression of five biomarkers, commonly involved in epithelial mesenchymal/mesenchymal epithelial transition (EMT/MET), in gastrointestinal stromal tumors (GISTs).
METHODS
In 80 consecutive GISTs the IHC examinations were performed using the EMT-related antibodies E-cadherin, N-cadherin, SLUG, V-set and immunoglobulin domain containing 1 (VSIG1) and CD44.
RESULTS
The positivity rate was 88.75% for SLUG, 83.75% for VSIG1, 36.25% for CD44 and 10% for N-cadherin. No correlation was noted between the examined markers and clinicopathological parameters. Nuclear positivity for SLUG and VSIG1 was observed in all cases with distant metastasis. The extra-gastrointestinal stromal tumors (e-GISTs) expressed nuclear positivity for VSIG1 and SLUG, with infrequent positivity for N-cadherin and CD44. The low overall survival was mainly dependent on VSIG1 negativity (P = 0.01) and nuclear positivity for SLUG and/or CD44.
CONCLUSION
GIST aggressivity may be induced by nuclear up-regulation of SLUG and loss or cytoplasm-to-nuclear translocation of VSIG1. SLUG and VSIG1 may act as activated nuclear transcription factors. The CD44, but not N-cadherin, might also have an independent prognostic value in these tumors. The role of the EMT/MET-related transcription factors in the evolution of GISTs, should be revisited with a larger dataset. This is the first study exploring the IHC pattern of VSIG1 in GISTs.
Core tip: In this paper we proved for the first time in the current literature the possible role of V-set and immunoglobulin domain containing 1 (VSIG1) in gastrointestinal stromal tumors (GISTs) in correlation with the expression of the other markers involved in the epithelial mesenchymal/mesenchymal epithelial transition. Based on the obtained results, we hypothesized that the GIST aggressivity may be induced by nuclear upregulation of SLUG and the loss or cytoplasm-to-nuclear translocation of VSIG1.
