Case Report
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jul 26, 2021; 9(21): 6102-6109
Published online Jul 26, 2021. doi: 10.12998/wjcc.v9.i21.6102
Unusual immunohistochemical “null” pattern of four mismatch repair proteins in gastric cancer: A case report
Meng Yue, Jun-Ying Liu, Yue-Ping Liu
Meng Yue, Jun-Ying Liu, Yue-Ping Liu, Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
Author contributions: Yue M collected the patient’s clinical data, performed literature review, and drafted the whole manuscript; Liu JY assisted in data collection and literature review; Liu YP helped revise the manuscript; all authors read and approved the final manuscript.
Informed consent statement: The patient provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no competing interests to report.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
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:
Corresponding author: Yue-Ping Liu, MD, PhD, Chief Doctor, Professor, Senior Scientist, Department of Pathology, The Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Shijiazhuang 050011, Hebei Province, China.
Received: March 17, 2021
Peer-review started: March 17, 2021
First decision: April 4, 2021
Revised: April 16, 2021
Accepted: May 19, 2021
Article in press: May 19, 2021
Published online: July 26, 2021

Immunohistochemical (IHC) staining for mismatch repair (MMR) proteins is useful for gastric cancer treatment and prognosis. Different IHC staining patterns reflect the complex biological phenomena underlying MMR deficiency. We herein report a rare IHC staining pattern of four MMR-related proteins in gastric cancer.


A “null” IHC staining pattern of four MMR-related proteins, including MLH1, PMS2, MSH2, and MSH6, in a 67-year-old male patient with gastric cancer pT3N3aM0 revealed promoter hypermethylation of MLH1. Next-generation sequencing showed that these four genes exhibited changes. One of these was the somatic mutation of the missing copy number in exon 14 of MSH2. Mutation analysis using peripheral blood showed no germline mutations in these four genes. The patient had no history of personal or family tumor history. We classified this case as sporadic. The patient returned to normal after operation, and there were no signs of tumor metastasis and recurrence. After six cycles of adjuvant chemotherapy, the patient was discharged in a stable condition. The patient had a mild reaction to chemotherapy and a good prognosis. At present, 16 mo after the operation, the patient's condition is stable.


Abnormal MMR protein expression, helpful for individualized follow-up care, helped identify a sporadic case lacking familial clinical management implications.

Keywords: Gastric cancer, Mismatch repair proteins, Next-generation sequencing, Sporadic, Family management, Case report

Core Tip: A “null” immunohistochemical staining pattern of mismatch repair (MMR) proteins was revealed, which helped identify this case as sporadic without familial clinical management implications. An in-depth understanding of the abnormal MMR expression is helpful for individualized follow-up treatment and assessment of prognosis.