{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T18:30:50Z","timestamp":1786559450752,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Gastric cancer develops through a multistep histopathological sequence known as the Correa cascade. Cyclooxygenase\u20102 (COX\u20102) and lipid peroxidation products such as 4\u2010hydroxy\u20102\u2010nonenal (4\u2010HNE) 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\u2010seven gastric tissue samples ranging from normal mucosa to intestinal\u2010type carcinoma were analyzed. Immunohistochemistry for COX\u20102, 4\u2010HNE\u2010protein adducts, and acrolein\u2010protein adducts was performed, with assessment of associations with clinical features, mismatch repair (MMR) status, and\n                    <jats:italic>Helicobacter pylori (H. pylori)<\/jats:italic>\n                    infection. COX\u20102 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 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). No statistically significant associations with the evaluated clinical parameters were identified, although the observed distribution in deficient MMR and\n                    <jats:italic>H. pylori<\/jats:italic>\n                    \u2010negative cases warrants further investigation. A progressive increase in 4\u2010HNE staining intensity was observed along the Correa cascade, peaking in intestinal metaplasia and carcinoma (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Acrolein displayed a heterogeneous pattern, with the highest levels in\n                    <jats:italic>H. pylori<\/jats:italic>\n                    \u2010negative chronic gastritis and no consistent association with neoplastic progression. The observed COX\u20102 localization shift and elevated 4\u2010HNE levels may represent potentially informative features associated with gastric malignant transformation. However, as COX\u20102 expression intensity was not quantitatively assessed in the present study, these findings should be interpreted as preliminary and require validation in larger cohorts.\n                  <\/jats:p>","DOI":"10.1002\/mc.70137","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T18:36:08Z","timestamp":1781548568000},"page":"1033-1042","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessing the Malignant Potential of Gastric Mucosa Disorders: A Pilot Study on Lipid Peroxidation End Products and COX\u20102 Detection by Immunohistochemistry"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9389-3351","authenticated-orcid":false,"given":"Ivan","family":"\u0160vagelj","sequence":"first","affiliation":[{"name":"Department of Pathology and Cytology General County Hospital Vinkovci Vinkovci Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morana","family":"Jaganjac","sequence":"additional","affiliation":[{"name":"Laboratory for Oxidative Stress, Division of Molecular Medicine Ruder Boskovic Institute Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/hygiene3030019"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-311685"},{"issue":"24","key":"e_1_2_11_5_1","first-page":"6735","article-title":"Human Gastric Carcinogenesis: A Multistep and Multifactorial Process\u2010 First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention","volume":"52","author":"Correa P.","year":"1992","journal-title":"Cancer Research"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-2980.2011.00550.x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2006.21.5.871"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1033"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2019.103634"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v13.i25.3466"},{"issue":"2","key":"e_1_2_11_11_1","first-page":"519","article-title":"Increased Expression of Cyclooxygenase\u20102 Protein in Human Gastric Carcinoma","volume":"6","author":"Lim H. 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