{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:03:20Z","timestamp":1791047000954,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"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":["Histopathology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>PAX8 immunohistochemistry (IHC) is often used to distinguish urothelial carcinomas (UCs) from tumours of renal and Mullerian origin. However, some UCs have been shown to be PAX8\u2010positive. This study investigates the frequency of PAX8\u2010positive conventional UCs of the urinary bladder without subtype morphology and\/or divergent differentiation and their molecular profiles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>One hundred and one consecutive transurethral resections of the urinary bladder from 2019 to 2022 with a diagnosis of conventional urothelial carcinoma (UC) without subtype morphology and\/or divergent differentiation were retrospectively reviewed. Representative sections were selected for whole\u2010slide PAX8 IHC (10336\u20101\u2010AP; polyclonal). Next\u2010generation sequencing (NGS) was performed on all PAX8\u2010positive cases and on a subset of PAX8\u2010negative cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PAX8 IHC was positive in 10% (10\/101) of cases. Twenty cases underwent NGS, including all 10 PAX8\u2010positive UCs. All PAX8\u2010positive UCs had\n                      <jats:italic>TERT<\/jats:italic>\n                      promoter mutations.\n                      <jats:italic>TSC1<\/jats:italic>\n                      alterations,\n                      <jats:italic>NOTCH1<\/jats:italic>\n                      loss and\n                      <jats:italic>WT1<\/jats:italic>\n                      loss were more frequent in the PAX8\u2010positive cases compared with the PAX8\u2010negative cases.\n                      <jats:italic>RB1<\/jats:italic>\n                      loss was not seen in the PAX8\u2010positive UCs, while it was present in 40% of the PAX8\u2010negative UCs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      A subset of conventional UCs of the urinary bladder without subtype morphology and\/or divergent differentiation are PAX8\u2010positive and have frequent alterations in\n                      <jats:italic>TERT<\/jats:italic>\n                      promoter,\n                      <jats:italic>TSC1<\/jats:italic>\n                      ,\n                      <jats:italic>NOTCH1<\/jats:italic>\n                      , and\n                      <jats:italic>WT1<\/jats:italic>\n                      , with an absence of\n                      <jats:italic>RB1<\/jats:italic>\n                      loss. PAX8 positivity should be interpreted with caution if UC is in the differential, and NGS could be helpful in diagnostic workups as this study shows PAX8\u2010positive UCs may have a distinct molecular profile.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/his.70112","type":"journal-article","created":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T04:24:40Z","timestamp":1770438280000},"page":"1315-1323","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>PAX8<\/scp>\n                    \u2010positive conventional urothelial carcinomas of the urinary bladder and their distinct molecular profiles \u2013 A clinicopathologic study of 101 consecutive cases with next\u2010generation sequencing in 20 cases"],"prefix":"10.1111","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1890-7424","authenticated-orcid":false,"given":"Sarah Mae","family":"Lammert","sequence":"first","affiliation":[{"name":"Department of Pathology The University of Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7041-823X","authenticated-orcid":false,"given":"Wendy","family":"Luo","sequence":"additional","affiliation":[{"name":"Pritzker School of Medicine The University of Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1490-7063","authenticated-orcid":false,"given":"Allen C","family":"Zhu","sequence":"additional","affiliation":[{"name":"Pritzker School of Medicine The University of Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0899-484X","authenticated-orcid":false,"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology The University of Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0455-9413","authenticated-orcid":false,"given":"Tatjana","family":"Antic","sequence":"additional","affiliation":[{"name":"Department of Pathology The University of Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1793-2732","authenticated-orcid":false,"given":"Jung Woo","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Pathology The University of Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjgh-2020-004128"},{"key":"e_1_2_11_3_1","volume-title":"Urinary and male genital Tumours","author":"Williamson SR","year":"2022"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.7189\/jogh.13.04109"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2012.10.008"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13752"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2025.105882"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31829e2525"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics13162641"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-024-03872-y"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2006.06.024"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e318216c112"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2019.09.012"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(96)80087-1"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1993.tb05890.x"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2011.3"},{"key":"e_1_2_11_17_1","first-page":"1015","article-title":"PAX8 expression in human bladder cancer","volume":"16","author":"Pellizzari L","year":"2006","journal-title":"Oncol. Rep."},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2012.239"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2022-0469-OA"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-020-0453-z"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-020-02212-9"},{"key":"e_1_2_11_22_1","first-page":"5394","article-title":"The detection of PAX8 in human upper urinary tract urothelial carcinoma","volume":"11","author":"Xiang H","year":"2018","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3181dc5e8a"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAP.0000000000000256"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2013.1121"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2011.04093.x"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2012.12.012"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2022-0493-RA"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2016-0414"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2016.07.012"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1015"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1113"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.abm2496"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.49.30678"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-017-0040-z"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04809-8"},{"key":"e_1_2_11_37_1","article-title":"Rewiring of master transcription factor cistromes during high\u2010grade serous ovarian cancer development","volume":"12","author":"Nameki R","year":"2023","journal-title":"elife"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2022.100866"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.path.2018.07.011"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.007"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euf.2014.11.002"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2014.01.009"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-16-0003"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-23-0816"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0095"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2004088"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2023.155008"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1310522110"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12894-023-01349-9"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2021.1915725"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-002127"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2022.40.16_suppl.e16532"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn098"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.27217"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4176"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-00934-y"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI78185"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu264"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2008.02.037"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.endmts.2023.100143"},{"key":"e_1_2_11_61_1","first-page":"675","article-title":"The WT1 gene \u2013 Its role in tumourigenesis and prospects for immunotherapeutic advances","volume":"28","author":"Lindstedt I","year":"2014","journal-title":"In Vivo"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2011.162"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.12405"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.70112","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/his.70112","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.70112","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T01:08:37Z","timestamp":1777511317000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.70112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,6]]},"references-count":62,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1111\/his.70112"],"URL":"https:\/\/doi.org\/10.1111\/his.70112","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,6]]},"assertion":[{"value":"2025-10-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}