{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T04:44:12Z","timestamp":1780461852988,"version":"3.54.1"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T00:00:00Z","timestamp":1694044800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013796","name":"Canadian Urological Association Scholarship Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013796","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012118","name":"Ontario Institute for Cancer Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012118","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Papillary renal cell carcinoma (PRCC) histologic subtyping is no longer recommended in the 2022 WHO classification. Currently, WHO\/ISUP nucleolar grade is the only accepted prognostic histologic parameter for PRCC. ABCC2, a renal drug transporter, has been shown to significantly predict outcomes in PRCC. In this study we evaluated the prognostic significance of ABCC2 IHC staining patterns in a large, multi\u2010institutional PRCC cohort and assessed the association of these patterns with ABCC2 mRNA expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We assessed 254 PRCCs for ABCC2 IHC reactivity patterns that were stratified into negative, cytoplasmic, brush\u2010border &lt;50%, and brush\u2010border \u226550%. RNA <jats:italic>in situ<\/jats:italic> hybridization (ISH) was used to determine the transcript level of each group. Survival analysis was performed with SPSS and GraphPad software. RNA\u2010ISH showed that the ABCC2 group with any brush\u2010border staining was associated with a significant increase in the transcript level, when compared to the negative\/cytoplasmic group (<jats:italic>P<\/jats:italic>\u2009=\u20090.034). Both ABCC2 groups with brush\u2010border &lt;50% (<jats:italic>P<\/jats:italic>\u2009=\u20090.024) and brush\u2010border \u226550% (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) were also associated with worse disease\u2010free survival (DFS) in univariate analysis. Multivariate analysis showed that only ABCC2 IHC brush\u2010border (&lt;50% and \u226550%) reactivity groups (<jats:italic>P<\/jats:italic>\u2009=\u20090.037 and <jats:italic>P<\/jats:italic>\u2009=\u20090.003, respectively), and high\u2010stage disease (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) had a DFS of prognostic significance. In addition, ABCC2 brush\u2010border showed significantly worse DFS in pT1a (<jats:italic>P<\/jats:italic>\u2009=\u20090.014), pT1 (<jats:italic>P<\/jats:italic>\u2009=\u20090.013), \u22644\u2009cm tumour (<jats:italic>P<\/jats:italic>\u2009=\u20090.041) and high stage (<jats:italic>P<\/jats:italic>\u2009=\u20090.014) groups, while a similar analysis with high WHO\/ISUP grade in these groups was not significant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>ABCC2 IHC brush\u2010border expression in PRCC correlates with significantly higher gene expression and also independently predicts survival outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.15042","type":"journal-article","created":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T06:16:05Z","timestamp":1694153765000},"page":"949-958","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["<scp>ABCC2<\/scp> brush\u2010border expression predicts outcome in papillary renal cell carcinoma: a multi\u2010institutional study of 254 cases"],"prefix":"10.1111","volume":"83","author":[{"given":"Vincent Francis","family":"Castillo","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology University of Toronto  Toronto ON Canada"},{"name":"Li Ka Shing Knowledge Institute, St.\u00a0Michael's Hospital  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Masoomian","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology University of Toronto  Toronto ON Canada"},{"name":"Department of Laboratory Medicine, Unity Health Toronto  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3142-8846","authenticated-orcid":false,"given":"Kiril","family":"Trpkov","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Alberta Precision Laboratories and University of Calgary  Calgary AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4528-3724","authenticated-orcid":false,"given":"Michelle","family":"Downes","sequence":"additional","affiliation":[{"name":"Anatomic Pathology, Precision Diagnostics &amp; Therapeutics Program Sunnybrook Health Sciences Centre  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7589-0453","authenticated-orcid":false,"given":"Fadi","family":"Brimo","sequence":"additional","affiliation":[{"name":"Department of Pathology McGill University Health Center  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8640-5786","authenticated-orcid":false,"given":"Theodorus","family":"van der Kwast","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology University of Toronto  Toronto ON Canada"},{"name":"Division of Pathology University Health Network  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George M","family":"Yousef","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology University of Toronto  Toronto ON Canada"},{"name":"Division of Pathology University Health Network  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraam","family":"Zakhary","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology University of Toronto  Toronto ON Canada"},{"name":"Li Ka Shing Knowledge Institute, St.\u00a0Michael's Hospital  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Rotondo","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Unity Health Toronto  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"Saad","sequence":"additional","affiliation":[{"name":"Li Ka Shing Knowledge Institute, St.\u00a0Michael's Hospital  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vy\u2010nhan","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Li Ka Shing Knowledge Institute, St.\u00a0Michael's Hospital  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wondwossen","family":"Kidanewold","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology University of Toronto  Toronto ON Canada"},{"name":"Department of Laboratory Medicine, Unity Health Toronto  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Streutker","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Unity Health Toronto  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corwyn","family":"Rowsell","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Unity Health Toronto  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malek","family":"Hamdani","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Unity Health Toronto  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1937-3101","authenticated-orcid":false,"given":"Rola M","family":"Saleeb","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology University of Toronto  Toronto ON Canada"},{"name":"Li Ka Shing Knowledge Institute, St.\u00a0Michael's Hospital  Toronto ON Canada"},{"name":"Department of Laboratory Medicine, Unity Health Toronto  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOU.0000000000001000"},{"key":"e_1_2_10_3_1","first-page":"9","article-title":"Precision medicine: an optimal approach to patient care in renal cell carcinoma","volume":"14","author":"Sharma R","year":"2022","journal-title":"Front. 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