{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:03:43Z","timestamp":1791241423212,"version":"4.1.0"},"reference-count":238,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Swedish Cancer Society","award":["23 2814 Pj"],"award-info":[{"award-number":["23 2814 Pj"]}]},{"name":"Swedish Cancer Society","award":["2021 JCK-3110"],"award-info":[{"award-number":["2021 JCK-3110"]}]},{"name":"Swedish Cancer Society","award":["9326"],"award-info":[{"award-number":["9326"]}]},{"name":"Kempestiftelserna","award":["23 2814 Pj"],"award-info":[{"award-number":["23 2814 Pj"]}]},{"name":"Kempestiftelserna","award":["2021 JCK-3110"],"award-info":[{"award-number":["2021 JCK-3110"]}]},{"name":"Kempestiftelserna","award":["9326"],"award-info":[{"award-number":["9326"]}]},{"name":"SARG (ELKE)\/National and Kapodistrian University of Athens (NKUA)","award":["23 2814 Pj"],"award-info":[{"award-number":["23 2814 Pj"]}]},{"name":"SARG (ELKE)\/National and Kapodistrian University of Athens (NKUA)","award":["2021 JCK-3110"],"award-info":[{"award-number":["2021 JCK-3110"]}]},{"name":"SARG (ELKE)\/National and Kapodistrian University of Athens (NKUA)","award":["9326"],"award-info":[{"award-number":["9326"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In the setting of pronounced inflammation, changes in the epithelium may overlap with neoplasia, often rendering it impossible to establish a diagnosis with certainty in daily clinical practice. Here, we discuss the underlying molecular mechanisms driving tissue response during persistent inflammatory signaling along with the potential association with cancer in the gastrointestinal tract, pancreas, extrahepatic bile ducts, and liver. We highlight the histopathological challenges encountered in the diagnosis of chronic inflammation in routine practice and pinpoint tissue-based biomarkers that could complement morphology to differentiate reactive from dysplastic or cancerous lesions. We refer to the advantages and limitations of existing biomarkers employing immunohistochemistry and point to promising new markers, including the generation of novel antibodies targeting mutant proteins, miRNAs, and array assays. Advancements in experimental models, including mouse and 3D models, have improved our understanding of tissue response. The integration of digital pathology along with artificial intelligence may also complement routine visual inspections. Navigating through tissue responses in various chronic inflammatory contexts will help us develop novel and reliable biomarkers that will improve diagnostic decisions and ultimately patient treatment.<\/jats:p>","DOI":"10.3390\/ijms25021251","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T09:46:39Z","timestamp":1705657599000},"page":"1251","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Diagnostic Challenges during Inflammation and Cancer: Current Biomarkers and Future Perspectives in Navigating through the Minefield of Reactive versus Dysplastic and Cancerous Lesions in the Digestive System"],"prefix":"10.3390","volume":"25","author":[{"given":"Ioannis S.","family":"Pateras","sequence":"first","affiliation":[{"name":"2nd Department of Pathology, \u201cAttikon\u201d University Hospital, Medical School, National and Kapodistrian University of Athens, 124 62 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Igea","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria de Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"},{"name":"Mobile Genomes, Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela (USC), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilias P.","family":"Nikas","sequence":"additional","affiliation":[{"name":"Medical School, University of Cyprus, 2029 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8743-7843","authenticated-orcid":false,"given":"Danai","family":"Leventakou","sequence":"additional","affiliation":[{"name":"2nd Department of Pathology, \u201cAttikon\u201d University Hospital, Medical School, National and Kapodistrian University of Athens, 124 62 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9502-7916","authenticated-orcid":false,"given":"Nektarios I.","family":"Koufopoulos","sequence":"additional","affiliation":[{"name":"2nd Department of Pathology, \u201cAttikon\u201d University Hospital, Medical School, National and Kapodistrian University of Athens, 124 62 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Argyro Ioanna","family":"Ieronimaki","sequence":"additional","affiliation":[{"name":"2nd Department of Pathology, \u201cAttikon\u201d University Hospital, Medical School, National and Kapodistrian University of Athens, 124 62 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5385-5665","authenticated-orcid":false,"given":"Anna","family":"Bergonzini","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Alfred Nobels All\u00e9 8, 141 52 Stockholm, Sweden"},{"name":"Department of Molecular Biology and Ume\u00e5 Centre for Microbial Research (UCMR), Ume\u00e5 University, 901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han Suk","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Seoul National University Hospital, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7039-4223","authenticated-orcid":false,"given":"Antonios","family":"Chatzigeorgiou","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical School, National and Kapodistrian University of Athens, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1209-0942","authenticated-orcid":false,"given":"Teresa","family":"Frisan","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Ume\u00e5 Centre for Microbial Research (UCMR), Ume\u00e5 University, 901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos","family":"Kittas","sequence":"additional","affiliation":[{"name":"Department of Histopathology, Biomedicine Group of Health Company, 156 26 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis G.","family":"Panayiotides","sequence":"additional","affiliation":[{"name":"2nd Department of Pathology, \u201cAttikon\u201d University Hospital, Medical School, National and Kapodistrian University of Athens, 124 62 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/BF01972401","article-title":"A brief survey of the history of inflammation","volume":"8","year":"1978","journal-title":"Agents Action"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Serhan, C.N., Brain, S.D., Buckley, C.D., Gilroy, D.W., Haslett, C., O\u2019Neill, L.A.J., Perretti, M., Rossi, A.G., and Wallace, J.L. 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