{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:52:25Z","timestamp":1786978345980,"version":"build-2736575974"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["410981386"],"award-info":[{"award-number":["410981386"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Pancreatic ductal adenocarcinoma (PDAC) subtyping typically relies on immunohistochemistry (IHC) staining for critical markers like HNF1A and KRT81, a labor\u2010intensive manual staining process that introduces variability. Virtual staining methods offer promising alternatives by generating synthetic IHC images from routine hematoxylin and eosin (H&amp;E) slides. However, most current approaches evaluate success by image quality measures rather than assessing diagnostically relevant features. Here, we introduce a novel cycleGAN framework utilizing a contrastive\u2010inspired approach trained on semipaired datasets derived from consecutive tissue sections. Our method significantly enhances PDAC subtyping accuracy based on synthetic IHC images generated from standard H&amp;E inputs, improving the classification F1\u2010score from 0.66 to 0.77 for KRT81 and from 0.61 to 0.73 for HNF1A, compared with classification directly on H&amp;E images. This approach also substantially outperforms baseline CycleGAN models. These results underscore the clinical potential of contrastive virtual staining to streamline PDAC diagnostics and improve their robustness. \u00a9 2025 The Author(s).\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6491","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T03:31:48Z","timestamp":1762313508000},"page":"89-98","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Contrastive virtual staining enhances deep learning\u2010based\n                    <scp>PDAC<\/scp>\n                    subtyping from H&amp;E\u2010stained tissue cores"],"prefix":"10.1002","volume":"268","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8305-6370","authenticated-orcid":false,"given":"Maximilian","family":"Fischer","sequence":"first","affiliation":[{"name":"German Cancer Research Center (DKFZ) Heidelberg, Division of Medical Image Computing  Heidelberg Germany"},{"name":"Medical Faculty Heidelberg University  Heidelberg Germany"},{"name":"German Cancer Consortium (DKTK), DKFZ Core Center Heidelberg  Heidelberg Germany"},{"name":"Research Campus M<sup>2<\/sup>OLIE  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0414-1797","authenticated-orcid":false,"given":"Alexander","family":"Muckenhuber","sequence":"additional","affiliation":[{"name":"Institute of Pathology, TUM School of Medicine and Health Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6187-3636","authenticated-orcid":false,"given":"Robin","family":"Peretzke","sequence":"additional","affiliation":[{"name":"German Cancer Research Center (DKFZ) Heidelberg, Division of Medical Image Computing  Heidelberg Germany"},{"name":"Medical Faculty Heidelberg University  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luay","family":"Farah","sequence":"additional","affiliation":[{"name":"Bridge Institute of Experimental Tumor Therapy (BIT), Division of Solid Tumor Translational Oncology (DKTK) and Department of Medical Oncology, West German Cancer Center, University Hospital Essen University of Duisburg\u2010Essen  Essen 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Image Computing  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenz","family":"Feineis","sequence":"additional","affiliation":[{"name":"German Cancer Research Center (DKFZ) Heidelberg, Division of Medical Image Computing  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanno","family":"Gao","sequence":"additional","affiliation":[{"name":"German Cancer Research Center (DKFZ) Heidelberg, Division of Medical Image Computing  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5397-814X","authenticated-orcid":false,"given":"Shuhan","family":"Xiao","sequence":"additional","affiliation":[{"name":"German Cancer Research Center (DKFZ) Heidelberg, Division of Medical Image Computing  Heidelberg Germany"},{"name":"Faculty of Mathematics and Computer Science Heidelberg University  Heidelberg 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Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7269-5433","authenticated-orcid":false,"given":"Katja","family":"Steiger","sequence":"additional","affiliation":[{"name":"Institute of Pathology, TUM School of Medicine and Health Technical University of Munich  Munich Germany"},{"name":"German Cancer Consortium (DKTK), partner site Munich, a partnership between DKFZ and School of Medicine and Health Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8772-4778","authenticated-orcid":false,"given":"Jens T","family":"Sieveke","sequence":"additional","affiliation":[{"name":"Bridge Institute of Experimental Tumor Therapy (BIT), Division of Solid Tumor Translational Oncology (DKTK) and Department of Medical Oncology, West German Cancer Center, University Hospital Essen University of Duisburg\u2010Essen  Essen Germany"},{"name":"German Cancer Consortium (DKTK), partner site Essen, a partnership between German Cancer Research Center (DKFZ) and University Hospital Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1817-2598","authenticated-orcid":false,"given":"Lukas","family":"Endr\u00f6s","sequence":"additional","affiliation":[{"name":"Institute for Diagnostic and Interventional Radiology, School of Medicine and Health, TUM University Hospital Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6039-6957","authenticated-orcid":false,"given":"Rickmer","family":"Braren","sequence":"additional","affiliation":[{"name":"German Cancer Consortium (DKTK), partner site Munich, a partnership between DKFZ and School of Medicine and Health Technical University of Munich  Munich Germany"},{"name":"Institute for Diagnostic and Interventional Radiology, School of Medicine and 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-2180"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/2056-4538.12377"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0901557"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41585-022-00684-0"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02856-4"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1109\/CVPR52729.2023.00326"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.media.2022.102559"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03141-0"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02857-3"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44222-023-00096-8"},{"key":"e_1_2_8_12_1","first-page":"1630","article-title":"Unpaired 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