Comprehensive Assessment of Immuno-oncology Biomarkers in Adenocarcinoma,Urothelial Carcinoma,and Squamous-cell Carcinoma of the Bladder |
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| Institution: | 1. Molecular Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt;2. Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt;3. Zoology Department, Faculty of Science, Cairo University, Giza, Egypt;4. Medical Biochemistry and Molecular Biology, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt;5. Biochemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October, Egypt;6. Inorganic Chemistry, Faculty of Science, Cairo University, Giza, Egypt;7. Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt |
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| Abstract: | BackgroundIn patients with rare histologies of bladder cancer, including adenocarcinoma of the bladder (ACB) and squamous-cell carcinoma (SCC), there are limited standard therapy options, defining an unmet medical need.ObjectiveIn this comparative comprehensive genomic profiling (CGP) study, genomic alterations (GAs), and immuno-oncology (IO) biomarkers have been analyzed.Design, setting, and participantsWithin the Foundation Medicine database, 143 cases with centrally reviewed pure ACB, 2142 with pure urothelial carcinoma (UC), and 83 with pure SCC were subjected to CGP. All patients developed advanced disease following a primary diagnosis of bladder cancer.InterventionCGP using a hybrid capture–based assay and immunohistochemistry (IHC).Outcome measurements and statistical analysisTumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA, and microsatellite instability (MSI) was determined on 114 loci. Programmed cell-death ligand-1 (PD-L1) expression was determined by IHC (Ventana SP-142 assay), with >1% tumor cells (TCs) or tumor-infiltrating lymphocytes (TILs) scoring positive.Results and limitationsPure ACB patients were younger and more often female than pure UC and pure SCC patients. UC and SCC had a significantly higher median TMB than ACB (p < 0.001). Rare CD274 (PD-L1) amplification cases were more frequently seen in SCC than in UC (5% vs 1%), and were not seen in ACB. MSI high status was very uncommon in all tumor types (0–1%). The frequencies of PD-L1 expression in both TCs and TILs was higher in UC and SCC (both 30%) than in ACB (18%). The results are limited by their retrospective nature and lack of clinical data annotation.ConclusionsDeep sequencing revealed significant differences in IO biomarkers among the three major subtypes of bladder carcinomas. UC and SCC revealed higher frequencies of PD-L1 expression and higher TMB than ACB, and SCC has the highest frequency of CD274 amplification. The presence of pure SCC features should not disqualify patients for inclusion in IO trials.Patient summaryTumor samples from patients diagnosed with advanced pure adenocarcinoma of the bladder (ACB) or pure squamous-cell carcinoma (SCC) have been analyzed in terms of frequency of putative immunotherapy biomarkers. The results indicated that pure SCC of the bladder was characterized by genomic features that portend similar response possibilities to immunotherapy compared with the classical pure urothelial carcinoma. Conversely, for pure ACB there might be different therapeutic opportunities, such as targeted therapies against peculiar genomic alterations in selected patients. |
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| Keywords: | Genomic alterations Bladder adenocarcinoma Bladder squamous-cell carcinoma Variant histologies Immunotherapy biomarkers |
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