In:
Journal of Clinical Pathology, BMJ, Vol. 75, No. 1 ( 2022-01), p. 39-44
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0021-9746
,
1472-4146
DOI:
10.1136/jclinpath-2020-207089
Language:
English
Publisher:
BMJ
Publication Date:
2022
detail.hit.zdb_id:
2028928-5