Clinical Significance of PD‐L1, LAG3, and VISTA in Patients With Poorly Cohesive Cell Gastric Cancer

초록

Background/Aim: Compared to other histological gastric cancer subtypes, poorly cohesive cells gastric cancer (PCC‑ GC) is characterized by a distinct set of epidemiological, histological, and clinical features requiring a specific diagnostic and therapeutic approach. This study analyzed the expression of programmed cell death protein ligand‑ 1 (PD‑L1), lymphocyte‑activation gene 3 (LAG3), and V‑domain suppressor of T cell activation (VISTA) and their impact on the survival of patients with PCC‑GC. Patients and Methods: We retrospectively collected 230 surgically resected stage II/III PCC‑GC cases. After LAG3, VISTA, and PD‑L1 immunostaining, VISTA expression was assessed in immune (ICs) and tumor cells (TCs). The clinicopathological and prognostic significance of these biomarkers were evaluated. Results: The median patient’s age was 60 years (range=31‑86 years). Additionally, 126 patients (54.8%) were males, and 104 patients (45.2%) were females. Ninety‑eight patients (42.6%) had stage II PCC‑GC, and 132 patients (57.4%) had stage III PCC‑GC. LAG3 over‑expression was observed in 9.6% of PCC‑GC cases. VISTA in ICs and PD‑L1 were over‑expressed in 73.0% and 13.9% of the cohort, respectively. Expression of VISTA in ICs was more frequently observed in stage III PCC‑GC (p=0.02). LAG3 and VISTA positivity in ICs served as favorable outcome indicators for disease‑free survival, although without statistically significant difference (p=0.054). PD‑L1 expression did not have a prognostic value in patients with PCC‑GC. Conclusion: VISTA‑IC positivity was significantly associated with the pathologic stage. Since a higher LAG3 and VISTA‑ IC expression showed a tendency to predict favorable patient outcomes, these immune‑related markers might serve as prognostic and therapeutic indicators for patients with PCC‑GC. © (2025), (International Institute of Anticancer Research). All rights reserved.

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