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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
BACKGROUND
Although the role of p53 in the evolution and prognosis of gastric cancer (GC) has been extensively examined, the exact mechanism of action is incompletely understood. In the last years, p53-target genes were supposed to be involved in the p53 pathway. One of them is the tumor-suppressor gene Maspin, which codifies the protein with the same name. Maspin activity depends on its subcellular localization. To our knowledge, the possible role of TP53 gene in Maspin subcellular localization, in GC cells, has not yet been studied in a large number of human samples.
AIM
To evaluate the possible role of wild-type and mutated p53 in Maspin subcellular localization.
METHODS
The present study included 266 consecutive patients with GC in which TP53 gene status, and mutations in exons 2 to 11, respectively, were analyzed and correlated with immunohistochemical expression of p53 and Maspin.
RESULTS
None of the 266 cases showed mutations in exon 9. The rate of TP53 mutations was 33.83%. The mutation rate was slightly higher in distally-located GCs, with a lower degree (≤ 5 buds/ high power fields) of dyscohesivity (P < 0.01). The wild-type cases had a longer survival, compared with mutant GCs, especially in patients without lymph node metastases, despite the high depth of tumor infiltration (P = 0.01). The Dukes-MAC-like staging system was proved to have the most significant independent prognostic value (P < 0.01). The statistical correlations proved that TP53 gene mutations in exon 7 might induce knockdown of Maspin, but wild-type p53 can partially restore nuclear Maspin expression and decrease the metastatic potential of gastric adenocarcinoma cells.
CONCLUSION
Downregulated Maspin might be induced by mutations in exon 7 of the TP53 gene but wild-type p53 can partially restore nuclear Maspin expression. These findings should be proved in experimental studies.
Core tip: In this paper we tried to emphasize the possible prognostic role of TP53 status in gastric cancer, and its relation with Maspin protease. For the first time, we have proved that TP53 gene mutations in exon 7 might induce knockdown of Maspin, but wild-type p53 can partialy restore nuclear Maspin expression and decrease the metastatic potential of gastric adenocarcinoma cells.
