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Updated: Oct 5, 2025
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Monitoring EBV infection, MSI, PDL-1 expression, Her-2/neu amplification as a biomarker for PD-1 inhibition in
Background:
The anti-PD-1 monoclonal antibody pembrolizumab has been shown to be associated with a good response in patients with metastatic gastric cancer. Excellent therapeutic results of pembrolizumab have been shown in patients with tumours showing a high microsatellite instability (MSI) and Epstein-Barr virus (EBV) positivity.
Goal:
This is a retrospective study of 40 bioptic specimens from the patients, who underwent gastrectomy for gastric carcinoma. The goal of the study was to identify biomarkers (EBV, MLH-1, PDL-1 expression) that are potentially relevant for selecting the patients, who may benefit from PD-1 inhibition therapy.
Methods:
Immunohistochemical (IHC) expression of PDL-1 and MSI, cytogenetic FISH amplification of the HER-2/neu gene and polymerase chain reaction of EBV RNA, including charge quantification, were performed in selected patients with metastatic or advanced gastric cancer.
Results:
EBV-encoded RNA was detected in nine patients. None of them exhibited Her-2 overexpression or CMV infection. PD-L1 was detected in twelve patients. Ten patients were MLH1 positive. All nine cases of EBV infection showed a high expression of PD-L1 and MLH-1 (Tab. 1, Ref. 14).
Insights
Pembrolizumab shows promise for metastatic gastric cancer, particularly in tumors with high microsatellite instability (MSI) and Epstein-Barr virus (EBV) positivity. Biomarker analysis identified EBV, PD-L1, and MLH-1 as key indicators for treatment selection.
Area of Science:
- Oncology
- Immunotherapy
- Gastroenterology
Background:
- Pembrolizumab, an anti-PD-1 antibody, demonstrates efficacy in metastatic gastric cancer.
- Tumors with high microsatellite instability (MSI) and Epstein-Barr virus (EBV) positivity respond well to pembrolizumab.
- Identifying predictive biomarkers is crucial for optimizing PD-1 inhibition therapy in gastric cancer.
Purpose of the Study:
- To identify biomarkers for patient selection in PD-1 inhibitor therapy for gastric cancer.
- Investigate the role of EBV, MLH-1, and PD-L1 expression as predictive markers.
- Analyze 40 bioptic specimens from gastric carcinoma patients undergoing gastrectomy.
Main Methods:
- Immunohistochemistry (IHC) for PD-L1 and MSI assessment.
- FISH for HER-2/neu gene amplification.
- Polymerase chain reaction (PCR) for EBV RNA detection and quantification.
Main Results:
- Epstein-Barr virus-encoded RNA (EBV) detected in 9 patients.
- PD-L1 expression observed in 12 patients; MLH-1 positivity in 10 patients.
- All 9 EBV-positive cases exhibited high PD-L1 and MLH-1 expression.
Conclusions:
- EBV positivity, alongside high PD-L1 and MLH-1 expression, may predict response to pembrolizumab in gastric cancer.
- These biomarkers are potentially relevant for selecting patients for PD-1 inhibition therapy.
- Further research is warranted to validate these findings in larger cohorts.
