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This study investigates the immunohistochemical expression of progastrin (hPG) and annexin A2 (ANXA2) and the polarization of tumor-associated macrophages in gastric adenocarcinoma to explore their potential prognostic and biological significance. Methods: A retrospective analysis was conducted on formalin-fixed, paraffin-embedded tissue samples from 60 patients with gastric adenocarcinoma (primary tumors, lymph node metastases, and non-tumoral gastric mucosa) and gastric biopsies from 23 healthy controls. The expression of hPG and ANXA2 was quantified using the H-score, and the CD163\/human leukocyte antigen\u2013DR (HLA-DR) ratio was used to represent macrophage polarization (M2\/M1). Statistical analyses included non-parametric tests, Spearman correlations, Kaplan-Meier survival curves, and Cox proportional-hazards models. Results: ANXA2 expression was significantly elevated in cancer cells from primary tumors and lymph node metastases, compared with the non-tumoral gastric mucosa tissues and gastric mucosa tissues from healthy controls. ANXA2 expression increased with the tumor grade. High ANXA2 levels were associated with shorter overall and disease-free survival, but they did not have independent prognostic value. Although hPG expression correlated positively with ANXA2, it showed no significant prognostic association. The CD163\/HLA-DR ratio increased with tumor progression and negatively correlated with ANXA2, but it did not influence survival outcomes. Conclusions: This study is the first to demonstrate the adverse prognostic impact of ANXA2 overexpression in gastric adenocarcinoma tissues from Caucasian patients. Our results suggest that ANXA2 might have utility as a prognostic biomarker and therapeutic target, if further large-scale studies validate and expand our findings.<\/jats:p>","DOI":"10.4132\/jptm.2025.12.20","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:18:07Z","timestamp":1773101887000},"page":"263-279","update-policy":"https:\/\/doi.org\/10.4132\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Progastrin, annexin A2, and tumor-associated macrophages in gastric 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