{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:11:42Z","timestamp":1792192302479,"version":"4.4.0"},"reference-count":46,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T00:00:00Z","timestamp":1765065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Gda\u0144sk Medical University","award":["ST 01-100024"],"award-info":[{"award-number":["ST 01-100024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Penile cancer (PeCa) is a rare malignancy with few validated tissue biomarkers to guide prognosis and treatment, despite growing evidence for a key role of inflammation in its biology. This retrospective study evaluated whether the immuno-expression of selected pro-inflammatory cytokines is associated with disease progression and cancer-specific survival (CSS) in PeCa. Immunohistochemistry (IHC) analysis of eight cytokines (IL-1A, IL-1B, IL-2, IL-6, IL-12, TGF-\u03b21, TNF-\u03b1 and IFN-\u03b3) was performed in paired tumour tissues and corresponding negative surgical margins from 94 patients with penile squamous cell carcinoma. Compared with surgical margins, tumour tissues showed a characteristic inflammatory shift, with markedly increased IL-1\u03b2 and IL-6 and relatively reduced TNF-\u03b1, IFN-\u03b3, IL-12 and IL-2. Receiver Operating Characteristic (ROC) analysis indicated that TNF-\u03b1, IL-6 and IL-12 had the strongest ability to discriminate tumour from normal tissue and provided data-driven cut-offs for subsequent analyses. Within tumour samples, high IL-1\u03b1, IL-12 and TGF-\u03b21 immuno-expression was significantly associated with advanced UICC TNM prognostic stage and lymph node involvement. Importantly, in contrast to the classically anti-tumour role of IL-12 described in many other solid cancers, increased IL-12 immuno-expression in tumour tissues in our cohort was independently associated with poorer CSS in multivariable Cox regression (HR 2.42, 95% CI: 1.08\u20135.41, p = 0.031), alongside advanced TNM stage (HR 5.03, 95% CI: 2.12\u201311.95, p = 0.0002). These findings highlight IL-1\u03b1, IL-12 and TGF-\u03b21 as promising tissue biomarkers of aggressive PeCa and support a central role for cytokine-driven immune dysregulation in penile cancer. The prognostic value of IL-12 should be considered exploratory and warrants validation in larger, multicentre cohorts.<\/jats:p>","DOI":"10.3390\/ijms262411829","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T08:21:43Z","timestamp":1765182103000},"page":"11829","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["IL-12 as a Potential Prognostic Marker in Penile Cancer: Implications for Immune Dysregulation"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2017-5417","authenticated-orcid":false,"given":"Mateusz","family":"Czajkowski","sequence":"first","affiliation":[{"name":"Department of Urology, Medical University of Gda\u0144sk, Mariana Smoluchowskiego 17 Street, 80-214 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9529-2381","authenticated-orcid":false,"given":"Micha\u0142","family":"Kunc","sequence":"additional","affiliation":[{"name":"Department of Pathomorphology, Medical University of Gda\u0144sk, Mariana Smoluchowskiego 17 Street, 80-214 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Kie\u017cun","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, Warszawska 30, 10-082 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3537-4710","authenticated-orcid":false,"given":"Bart\u0142omiej Emil","family":"Krazi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, Warszawska 30, 10-082 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Matuszewski","sequence":"additional","affiliation":[{"name":"Department of Urology, Medical University of Gda\u0144sk, Mariana Smoluchowskiego 17 Street, 80-214 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2549-9054","authenticated-orcid":false,"given":"Weronika","family":"\u0141yzi\u0144ska","sequence":"additional","affiliation":[{"name":"ED Scientific Circle of Pathomorphology, Medical University of Gda\u0144sk, D\u0119binki, 80-211 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver W.","family":"Hakenberg","sequence":"additional","affiliation":[{"name":"Department of Urology, Jena University Hospital, 07747 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4310-1616","authenticated-orcid":false,"given":"Piotr M.","family":"Wierzbicki","sequence":"additional","affiliation":[{"name":"Department of Histology, Medical University of Gda\u0144sk, D\u0119binki, 80-211 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41572-021-00246-5","article-title":"Penile Cancer","volume":"7","author":"Thomas","year":"2021","journal-title":"Nat. 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