Assessing the Malignant Potential of Gastric Mucosa Disorders: A Pilot Study on Lipid Peroxidation End Products and...

Gastric cancer develops through a multistep histopathological sequence known as the Correa cascade. Cyclooxygenase-2 (COX-2) and lipid peroxidation products such as 4-hydroxy-2-nonenal (4-HNE) and acrolein are implicated in gastric tumorigenesis through inflammation and oxidative stress, but their expression dynamics across disease stages remain unclear. This pilot study evaluated their immunohistochemical expression along the modified Correa cascade to explore their diagnostic relevance. Fifty-seven gastric tissue samples ranging from normal mucosa to intestinal-type carcinoma were analyzed. Immunohistochemistry for COX-2, 4-HNE-protein adducts, and acrolein-protein adducts was performed, with assessment of associations with clinical features, mismatch repair (MMR) status, and Helicobacter pylori (H. pylori) infection. COX-2 showed consistent membranous staining in normal mucosa, chronic gastritis, and intestinal metaplasia, with a significant shift to cytoplasmic or perinuclear localization, or complete loss, in atrophic gastritis and carcinoma (p < 0.001). No statistically significant associations with the evaluated clinical parameters were identified, although the observed distribution in deficient MMR and H. pylori-negative cases warrants further investigation. A progressive increase in 4-HNE staining intensity was observed along the Correa cascade, peaking in intestinal metaplasia and carcinoma (p < 0.001). Acrolein displayed a heterogeneous pattern, with the highest levels in H. pylori-negative chronic gastritis and no consistent association with neoplastic progression. The observed COX-2 localization shift and elevated 4-HNE levels may represent potentially informative features associated with gastric malignant transformation. However, as COX-2 expression intensity was not quantitatively assessed in the present study, these findings should be interpreted as preliminary and require validation in larger cohorts.