{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:37:38Z","timestamp":1787017058349,"version":"build-2736575974"},"reference-count":23,"publisher":"BMJ","issue":"1","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2020,10,15]]},"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>According to The Cancer Genome Atlas (TCGA), around 9% of bladder carcinomas usually show abnormalities of the murine double minute 2 (MDM2) gene, but a few studies have been investigated them. We profiled MDM2 gene amplification in a series of urothelial carcinomas (UC) considering the molecular subtypes and expression of programmed death ligand 1 (PD-L1).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>117 patients with muscle-invasive UC (pT2-3) without (N0) or with (N+) lymph-node metastases were revised. Only cases with availability of in toto specimens and follow-up were studied. Tissue microarray was built. p53, ER, RB1, GATA-3, CK20, CK5\/6, CD44 and PD-L1 (clone sp263) immunoexpression was evaluated. Fluorescent in situ hybridisation was assessed by using the HER-2\/neu, FGFR-3, CDKN2A and MDM2 probes. True (ratio 12q\/CEP12 &gt;2) MDM2 gene amplification was distinguished from polyploidy\/gains (ratio &lt;2, absolute copy number of MDM-2 &gt;2). MDM2 and PD-L1 values were correlated to the TCGA molecular phenotypes. Statistical analysis was performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>6\/50 (12%) cases (5 N0 and 1 N+) were amplified for MDM2 without matching to molecular phenotypes. Of 50, 14 (37%) cases expressed PD-L1 at 1% cut-off; 3\/50 (9%) at &gt;50% cut-off; of these, 2 cases on side of neoplasia among inflammatory cells. Only one out of six (17%) cases amplified for MDM2 showed expression (&gt;50% cut-off) of PD-L1. MDM2 amplification was independent to all documented profiles (k test=0.3) and was prevalent in recurrent UC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MDM2 amplification has been seen in both PD-L1 positive and negative muscle-invasive bladder UC independently from the TCGA molecular phenotypes. MDM2 and PD-L1 might be assessed in order to predict a better response to combo\/single targeted therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jclinpath-2020-207089","type":"journal-article","created":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T17:20:54Z","timestamp":1604424054000},"page":"39-44","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["MDM2 gene amplification as selection tool for innovative targeted approaches in PD-L1 positive or negative muscle-invasive urothelial bladder carcinoma"],"prefix":"10.1136","volume":"75","author":[{"given":"Matteo","family":"Brunelli","sequence":"first","affiliation":[{"name":"Department of Diagnostics and Public Health, Pathology Unit, University and Hospital Trust of Verona, Verona, Italy"},{"name":"Department of Diagnostics and Public Health, FISH Lab, University and Hospital Trust of Verona, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Tafuri","sequence":"additional","affiliation":[{"name":"Division of Urology, University and Hospital Trust of Verona, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3180-5843","authenticated-orcid":false,"given":"Luca","family":"Cima","sequence":"additional","affiliation":[{"name":"Department of Clinical Services, Pathology Unit, Santa Chiara Hospital, Trento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Angela","family":"Cerruto","sequence":"additional","affiliation":[{"name":"Division of Urology, University and Hospital Trust of Verona, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Milella","sequence":"additional","affiliation":[{"name":"Division of Oncology, University and Hospital Trust of Verona, Verona, 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5107-1584","authenticated-orcid":false,"given":"Valerio Gaetano","family":"Vellone","sequence":"additional","affiliation":[{"name":"Division of Oncology, San Martino Hospital, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Elena","family":"Rebuzzi","sequence":"additional","affiliation":[{"name":"Division of Oncology, San Martino Hospital, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Procopio","sequence":"additional","affiliation":[{"name":"Division of Oncology, IRCCS Foundation, Istituto Nazionale dei Tumori di Milano, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Verzoni","sequence":"additional","affiliation":[{"name":"Division of Oncology, IRCCS Foundation, Istituto Nazionale dei Tumori di Milano, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Bracarda","sequence":"additional","affiliation":[{"name":"Division of Oncology, Santa Maria Hospital, Terni, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Sabbatini","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hematology & Respiratory Diseases, Division of Oncology, University of Modena & Reggio Emilia, Modena, Modena & Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Baldessari","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hematology & Respiratory Diseases, Division of Oncology, University of Modena & Reggio Emilia, Modena, Modena & Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albino","family":"Eccher","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Public Health, Pathology Unit, University and Hospital Trust of Verona, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodolfo","family":"Passalacqua","sequence":"additional","affiliation":[{"name":"Division of Oncology, Hospital Trust of Cremona, Cremona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Perrucci","sequence":"additional","affiliation":[{"name":"Division of Oncology, Hospital Trust of Cremona, Cremona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Olga","family":"Giganti","sequence":"additional","affiliation":[{"name":"Division of Oncology, Hospital Trust of Cremona, Cremona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddalena","family":"Donini","sequence":"additional","affiliation":[{"name":"Division of Oncology, Hospital Trust of Cremona, Cremona, 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