In this study, we aimed to identify prognostic factors of cancer mortality in patients who received radical cystectomy and to identify genomic alterations in a sub-cohort of patients with locally advanced (pT3-4) and/or positive lymph nodes bladder cancer (BC).
We collected 101 BC samples from 2010 to 2018 who previously received radical cystectomy. Immunohistochemical slides were evaluated for PPAR, cAMP, IMP3, Ki67, CDK4, POU5F1, Cyclin E and MDM2, p65, CD3, CD4, CD8, CD20, CD68, CD163, FOXP3, PD-1 and PD-L1 expression. We calculated a prognostic score (PS) based on the positivity to PD-1, PD-L1 and of cAMP (final score ranging from 0 to 3). DNA of each sample have been used for sequencing by NGS in a sub-cohort of 6 patients with locally advanced (pT3-4) and/or positive lymph nodes BC.
PD-1 + (HR [hazard ratio] 2.59; p = 0.04), PD-L1+ (HR = 6.46; p < 0.01) and cAMP+ (HR 3.04; p = 0.02) were independent predictors of cancer-specific mortality (CSM). Increase of PS (score = 0 as reference) was associated with CSM, 0.81 (p = 0.80), 4.72 (p = 0.01) and 10.51 (p < 0.0) for PS 1, 2 and 3, respectively. ERBB2 was the gene most frequently mutated.
BC exhibited heterogenous protein expression and variable genomic features. Identification of expression of PD-1, PD-L1 and cAMP could help in predicting oncological outcomes.
Journal of cancer research and clinical oncology. 2022 Aug 16 [Epub ahead of print]
Giorgio Ivan Russo, Nicolò Musso, Arturo Lo Giudice, Maria Giovanna Asmundo, Marina Di Mauro, Paolo G Bonacci, Mariacristina Massimino, Dalida Bivona, Stefania Stefani, Elisabetta Pricoco, Matteo Ferro, Massimo Camarda, Sebastiano Cimino, Giuseppe Morgia, Rosario Caltabiano, Giuseppe Broggi
Urology Section, Department of Surgery, University of Catania, 95123, Catania, Italy. ., Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, 95123, Catania, Italy., Urology Section, Department of Surgery, University of Catania, 95123, Catania, Italy., Department of Medical and Surgical Sciences and Advanced Technologies "G. F. Ingrassia", Anatomic Pathology, University of Catania, 95123, Catania, Italy., Department of Urology, European Institute of Oncology, IRCCS, Milan, Italy., STLab S.R.L., Catania, Italy.