PT  - JOURNAL ARTICLE
AU  - Matteo Brunelli
AU  - Alessandro Tafuri
AU  - Luca Cima
AU  - Maria Angela Cerruto
AU  - Michele Milella
AU  - Andrea Zivi
AU  - Sebastiano Buti
AU  - Melissa Bersanelli
AU  - Giuseppe Fornarini
AU  - Valerio Gaetano Vellone
AU  - Sara Elena Rebuzzi
AU  - Giuseppe Procopio
AU  - Elena Verzoni
AU  - Sergio Bracarda
AU  - Roberto Sabbatini
AU  - Cinzia Baldessari
AU  - Albino Eccher
AU  - Rodolfo Passalacqua
AU  - Bruno Perrucci
AU  - Maria Olga Giganti
AU  - Maddalena Donini
AU  - Stefano Panni
AU  - Marcello Tucci
AU  - Veronica Prati
AU  - Cinzia Ortega
AU  - Anna Caliò
AU  - Filippo Alongi
AU  - Enrico Munari
AU  - Giovanni Pappagallo
AU  - Roberto Iacovelli
AU  - Alessandra Mosca
AU  - Camillo Porta
AU  - Guido Martignoni
AU  - Alessandro Antonelli
TI  - MDM2 gene amplification as selection tool for innovative targeted approaches in PD-L1 positive or negative muscle-invasive urothelial bladder carcinoma
AID  - 10.1136/jclinpath-2020-207089
DP  - 2022 Jan 01
TA  - Journal of Clinical Pathology
PG  - 39--44
VI  - 75
IP  - 1
4099  - http://jcp.bmj.com/content/75/1/39.short
4100  - http://jcp.bmj.com/content/75/1/39.full
SO  - J Clin Pathol2022 Jan 01; 75
AB  - Aims 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).Methods 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 >2) MDM2 gene amplification was distinguished from polyploidy/gains (ratio <2, absolute copy number of MDM-2 >2). MDM2 and PD-L1 values were correlated to the TCGA molecular phenotypes. Statistical analysis was performed.Results 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 >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 (>50% cut-off) of PD-L1. MDM2 amplification was independent to all documented profiles (k test=0.3) and was prevalent in recurrent UC.Conclusion 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.No data are available.