{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T14:38:59Z","timestamp":1786113539062,"version":"build-2736575974"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100018722","name":"Jaap Schouten Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018722","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The pathogenesis of intraductal carcinoma (IDC) is still controversial. Contrary to current opinion, where IDC represents retrograde spread of invasive prostate cancer (PCa), we recently presented an alternative, unifying hypothesis named \u2018Repetitive Invasion, Precursor Progression\u2019 (RIPP). Little is known about genomic alterations in high\u2010grade Prostatic Intraepithelial Neoplasia (HGPIN), IDC and adjacent invasive PCa. Our objective was to clarify the mutual clonal relationships among HGPIN, IDC, and adjacent PCa using spatial transcriptomics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Regions of interest containing HGPIN, IDC and adjacent invasive PCa were selected from six Gleason score 3\u2009+\u20094\u2009=\u20097 radical prostatectomy specimens. Spatial transcriptomic profiling and library preparation were executed according to the Visium workflow. Pathologist\u2010guided manual annotations were utilized to delineate regions of interest for the integrated analysis of chromosomal copy number variants (CNV) and spatiotemporal trajectories. Adjacent HGPIN, IDC and invasive PCa shared common CNV signatures across all samples, with various subclonal events. Unsupervised clonal analysis revealed that across three samples, the adjacent invasive subclone had acquired additional genomic alterations. In two samples, HGPIN, IDC and adjacent invasive PCa had identical CNVs. Finally, in one sample, IDC had additional CNVs compared with HGPIN and invasive glands. Supervised trajectory analysis consistently placed adjacent invasive PCa as the final step in the trajectory, after HGPIN and\/or IDC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Spatial transcriptomics revealed strong clonal relationships among adjacent HGPIN, IDC and invasive PCa. Supervised trajectory analysis did not support retrograde spread in this limited number of samples, while unsupervised analysis revealed a complex mutual relationship among HGPIN, IDC and adjacent PCa.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/his.70188","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T01:14:43Z","timestamp":1780535683000},"page":"429-441","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatial transcriptomics reveals clonal relationships between intraductal carcinoma and adjacent invasive prostate cancer"],"prefix":"10.1111","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6269-3002","authenticated-orcid":false,"given":"Hridya","family":"Harikumar","sequence":"first","affiliation":[{"name":"Department of Pathology and Clinical Bioinformatics Erasmus MC Cancer Institute, University Medical Centre  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8747-1494","authenticated-orcid":false,"given":"Myrthe","family":"de Waard\u2010van Baardwijk","sequence":"additional","affiliation":[{"name":"Department of Pathology and Clinical Bioinformatics Erasmus MC Cancer Institute, University Medical Centre  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3612-0024","authenticated-orcid":false,"given":"Marit","family":"de Haan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Clinical Bioinformatics Erasmus MC Cancer Institute, University Medical Centre  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0283-7069","authenticated-orcid":false,"given":"Gregory","family":"van Beek","sequence":"additional","affiliation":[{"name":"Department of Hematology Erasmus MC Cancer Institute, University Medical Centre  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3664-8616","authenticated-orcid":false,"given":"Karishma","family":"Lila","sequence":"additional","affiliation":[{"name":"Department of Pathology and Clinical Bioinformatics Erasmus MC Cancer Institute, University Medical Centre  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6814-0996","authenticated-orcid":false,"given":"Martin E","family":"van Royen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Clinical Bioinformatics Erasmus MC Cancer Institute, University Medical Centre  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7223-4565","authenticated-orcid":false,"given":"Thierry PP","family":"van den Bosch","sequence":"additional","affiliation":[{"name":"Department of Pathology and Clinical Bioinformatics Erasmus MC Cancer Institute, University Medical Centre  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8575-9213","authenticated-orcid":false,"given":"Mathijs A","family":"Sanders","sequence":"additional","affiliation":[{"name":"Department of Hematology Erasmus MC Cancer Institute, University Medical Centre  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9502-669X","authenticated-orcid":false,"given":"Eric","family":"Bindels","sequence":"additional","affiliation":[{"name":"Department of Hematology Erasmus MC Cancer Institute, University Medical Centre  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9817-9982","authenticated-orcid":false,"given":"Andrew","family":"Stubbs","sequence":"additional","affiliation":[{"name":"Department of Pathology and Clinical Bioinformatics Erasmus MC Cancer Institute, University Medical Centre  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2176-9102","authenticated-orcid":false,"given":"Geert JLH","family":"van Leenders","sequence":"additional","affiliation":[{"name":"Department of Pathology and Clinical Bioinformatics Erasmus MC Cancer Institute, University Medical Centre  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000002430"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000001290"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4628"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-017-3976-z"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.15414"},{"key":"e_1_2_11_7_1","unstructured":"10x Genomics.CytAssist Spatial Gene Expression Documentation [Internet].2025.https:\/\/www.10xgenomics.com\/support\/cytassist\u2010spatial\u2010gene\u2010expression\/documentation."},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-50904-x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05023-2"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43120-6"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-1977"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-1423"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00184607"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2014.03.009"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-017-1235-6"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2016.49"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2020-0015-RA"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001497"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5283"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2023.05.004"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-021-08593-y"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.24353"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8863"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.15354"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.15551"},{"key":"e_1_2_11_26_1","unstructured":"10x Genomics.Visium Spatial Assays | 10x Genomics [Internet].https:\/\/www.10xgenomics.com\/platforms\/visium\/product\u2010family."}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.70188","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/his.70188","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.70188","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T19:41:38Z","timestamp":1785958898000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.70188"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,3]]},"references-count":25,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/his.70188"],"URL":"https:\/\/doi.org\/10.1111\/his.70188","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,3]]},"assertion":[{"value":"2026-03-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}