Paradoxical expression pattern of the epithelial mesenchymal transition-related biomarkers CD44, SLUG, N-cadherin and VSIG1/Glycoprotein A34 in gastrointestinal stromal tumors

doi:10.4251/wjgo.v9.i11.436

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World Journal of Gastrointestinal Oncology

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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.

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.

Keywords: SLUG; Glycoprotein A34; N-cadherin; V-set and immunoglobulin domain containing gastrointestinal stromal tumors

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.