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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2020; 12(7): 741-755
Published online Jul 15, 2020. doi: 10.4251/wjgo.v12.i7.741
Maspin subcellular expression in wild-type and mutant TP53 gastric cancers
Simona Gurzu, Ioan Jung, Haruhiko Sugimura, Raluca Ioana Stefan-van Staden, Hidetaka Yamada, Hiroko Natsume, Yuji Iwashita, Rita Szodorai, Janos Szederjesi
Simona Gurzu, Ioan Jung, Rita Szodorai, Department of Pathology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology, Targu Mureș 540139, Mureș, Romania
Simona Gurzu, Research Center, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology, Targu Mureș 540139, Mureș, Romania
Haruhiko Sugimura, Hidetaka Yamada, Hiroko Natsume, Yuji Iwashita, Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
Raluca Ioana Stefan-van Staden, National Institute of Research for Electrochemistry and Condensed Matter, Bucharest 060021, Romania
Janos Szederjesi, Intensive Care Unit, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology, Targu Mureș 540139, Mureș, Romania
Author contributions: Gurzu S drafted the article and contributed to the histopathological diagnosis; Jung I contributed to the diagnosis and immunohistochemical assessment; Stefan-van Staden RI conferred the funding approval and supervised the scientific grant development; Sugimura H and Yamada H performed determinations of the p53 gene expression; Natsume H and Iwashita Y contributed to molecular examination; Szodorai R contributed to selection of patients and follow-up; Szederjesi J designed the statistical assessment and conferred the final agreement for publication. Gurzu S and Jung I contributed equally to the paper.
Supported by the Romanian National Authority for Scientific Research, No. 20 PCCF/2018.
Institutional review board statement: The Ethical Approval of Mureș County Emergency Hospital was obtained to perform the present study.
Informed consent statement: This is a retrospective study. No signed consent was necessary.
Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/
Corresponding author: Simona Gurzu, MD, PhD, Chief Doctor, Director, Full Professor, Research Fellow, Research Scientist, Department of Pathology, University of Medicine, Pharmacy, Sciences and Technology, 38 Gheorghe Marinescu Street, Targu Mureș 530193, Mureș, Romania. simonagurzu@yahoo.com
Received: February 4, 2020
Peer-review started: February 4, 2020
First decision: March 24, 2020
Revised: April 6, 2020
Accepted: May 27, 2020
Article in press: May 27, 2020
Published online: July 15, 2020
ARTICLE HIGHLIGHTS
Research background
Maspin is a serine protease that has been extensively studied by our team using immunostaining in gastric cancer (GC) and colorectal cancer samples. Our previous data, which are in line with literature data, showed that the role of Maspin is strongly dependent on its subcellular expression. In GC cells, Maspin downregulation increases the metastatic potential, cytoplasmic localization induces a better prognosis and nuclear staining is correlated with a higher local invasion.
Research motivation
As data on the correlation between Maspin and p53 are scarce in GC, the aim of this study was to determine the particular features of this possible interaction.
Research objectives
We compared immunohistochemical (IHC) staining of p53 and a p53 gene-related protein Maspin in GCs, and correlated the results with the TP53 gene expression profile. The independent prognostic values of the examined parameters were also determined.
Research methods
In 266 consecutive GC samples, we performed IHC staining with Maspin and p53 antibodies, and performed sequencing (from paraffin-embedded tissues), to determine TP53 gene mutations in exons 2 to 11.
Research results
In the examined cohort, the TP53 gene mutation rate was 33.83%, and no correlation with the immunoexpression of p53 protein was observed. Wild-type cases, especially those without lymph node metastases, had a better survival rate. The most significant independent prognostic parameter proved to be the Dukes-MAC-like tumor stage. Statistical correlations proved that Maspin nuclear restoration, in the invasion front, can be obtained in TP53 wild-type cases, whereas mutations in exon 7 of the TP53 gene induce Maspin negativity, in both the tumor core and invasion area.
Research conclusions
Despite several prognostic parameters proposed for GC, the survival rate is better predicted by the classic TN stage. Downregulated Maspin might be induced by mutations in exon 7 of the TP53 gene but wild-type p53 can partially restore nuclear Maspin expression.
Research perspectives
As the possible role of mutations in exon 7 of the TP53 gene was proved for the first time in the present study, following downregulation of Maspin, further investigations are necessary to elucidate the possible therapeutic role of anti-Maspin chemical derivates.
