PD-L1 expression in gastroesophageal dysplastic lesions

Area of Science:

• Oncology
• Gastroenterology
• Immunology

Background:

• Immunotherapy is approved for gastric (GC) and gastroesophageal-junction adenocarcinomas (GEC).
• PD-L1 expression is a potential predictive biomarker in these cancers.
• Gastroesophageal dysplasia is a precursor to GC and GEC.

Purpose of the Study:

• To investigate PD-L1 expression and DNA mismatch repair (MMR) status in gastroesophageal dysplastic lesions.
• To assess the correlation between PD-L1 status and clinicopathological features of dysplasia.
• To compare PD-L1 expression in dysplastic lesions with matched invasive tumors.

Main Methods:

• Analysis of 125 gastroesophageal dysplastic lesions (52 low-grade, 73 high-grade) for PD-L1 and MMR protein status.
• PD-L1 evaluation using immunohistochemistry with combined positive score (CPS) ≥ 1.
• Comparison of PD-L1 status between dysplastic and matched invasive lesions (30 pairs).

Main Results:

• PD-L1 positivity (CPS ≥ 1) was observed in 48 (31.0%) dysplastic lesions.
• Higher PD-L1 prevalence in esophageal vs. gastric specimens, high-grade vs. low-grade dysplasia, and MMR-deficient lesions.
• Discordant PD-L1 status was found in 40% (12/30) of matched dysplastic and invasive lesions.

Conclusions:

• A significant prevalence of PD-L1 positivity exists in gastroesophageal dysplastic lesions.
• PD-L1 status in dysplasia may inform future immunotherapy strategies.
• The discordance in PD-L1 status between dysplasia and invasive cancer highlights the need for careful biomarker assessment.