Gastritis cystica profunda is associated with aberrant p53 and Epstein–Barr virus in gastric cancer: A clinicopathological, immunohistochemical and in situ hybridization study

Abstract

Gastritis cystica profunda (GCP) is a lesion characterized by cystic gastric glands within the submucosa. Some studies have reported that GCP is a precancerous lesion. Here, we investigated the association between GCP and gastric cancer. Gastric cancer specimens were taken from 1432 patients undergoing surgery or endoscopic submucosal resection and were classified as GCP or non‐GCP. The clinicopathological features, immunohistochemistry and in situ hybridization expression of p53, Ki‐67, KCNE2, Epstein–Barr virus (EBV) and programmed death ligand 1 (PD‐L1) were compared between the two groups, as well as between GCPs and normal pyloric glands. One hundred and eighty patients (12.6%) had GCPs. In the GCP group, no cancerous lesions were found within the GCPs, but 13% were linked to GCPs and 60.2% were located above or near GCPs. Aberrant p53 expression, EBV‐positive cancer cells and PD‐L1 scores were significantly higher in the GCP group. The p53 score and Ki‐67 labelling index were significantly higher and the KCNE2 score was significantly lower in GCPs than in pyloric glands. Although we suggest GCP is paracancerous, GCP has high proliferation activity and gastric cancer with GCP is associated with aberrant p53 and EBV. GCP is associated with aberrant p53 expression and EBV.

The Association of EBV and Gastric Cancer

“…Previous research studies with small sample sizes have revealed similar ndings. However, no signi cant differences were observed 6, 10,11 . The present study demonstrated that the survival time of EBV positive patients was longer than that of EBV negative patients.…”

“…Its infection rate in humans can reach 90% or higher 5,8,[10][11][12][13][14] . At present, the mechanism of the EBVmediated gastric mucosal epithelium infection has been described as follows: Initially, EBV infects B lymphocytes and oral epithelial cells; subsequently, EBV is reactivated in B lymphocytes in the stomach and released to infect epithelial cells 5, 8, 10-14 .…”

Update S2k-Guideline Helicobacter pylori and gastroduodenal ulcer disease of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS)

“…These rare causes include: Crohn's disease, eosinophilic gastroduodenitis, systemic mastocytosis, vasculitis and ischemia, as well as tumours (e. g. gastrinomas), metastases and other consuming diseases. In immunocompromised or immunosuppressed patients (HIV infection, after organ transplan-tation), viral infections or reactivations (CMV, EBV, HSV) with gastroduodenal ulcers occur more frequently [563][564][565][566]. Increased exposure to radiation from a previous radiotherapy or internal radiotherapy (e. g. as part of selective internal radiotherapy (SIRT)) can cause gastrointestinal ulcers throughout the gastrointestinal tract [567][568][569][570][571][572].…”

Aktualisierte S2k-Leitlinie Helicobacter pylori und gastroduodenale Ulkuskrankheit der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – Juli 2022 – AWMF-Registernummer: 021–001

“…B. Gastrinome), Metastasen und andere konsumierende Erkrankungen. Bei immunkompromittierten oder immunsuppressiv behandelten Patienten (HIV-Infektion, nach Organtransplantation) treten gehäuft virale Infektionen oder Reaktivierungen (CMV, EBV, HSV) mit gastroduodenalen Ulzera auf [562][563][564][565]. Eine erhöhte Exposition im Strahlenfeld einer erfolgten Radiotherapie oder durch interne Radiotherapie (z.…”