Immunotherapy in Penile Squamous Cell Carcinoma: Present or Future? Multi-Target Analysis of Programmed Cell Death Ligand 1 Expression and Microsatellite Instability.

Autor:	Montella M; Pathology Unit, Department of Mental Health, Physic and Preventive Medicine University of Campania 'Luigi Vanvitelli', Naples, Italy., Sabetta R; Pathology Unit, Department of Mental Health, Physic and Preventive Medicine University of Campania 'Luigi Vanvitelli', Naples, Italy., Ronchi A; Pathology Unit, Department of Mental Health, Physic and Preventive Medicine University of Campania 'Luigi Vanvitelli', Naples, Italy., De Sio M; Urology Unit, Department of Woman Child and of General and Specialist Surgery, University of Campania 'Luigi Vanvitelli', Naples, Italy., Arcaniolo D; Urology Unit, Department of Woman Child and of General and Specialist Surgery, University of Campania 'Luigi Vanvitelli', Naples, Italy., De Vita F; Oncology Unit, Department of Precision Medicine, University of Campania 'Luigi Vanvitelli', Naples, Italy., Tirino G; Oncology Unit, Department of Precision Medicine, University of Campania 'Luigi Vanvitelli', Naples, Italy., Caputo A; Department of Medicine and Surgery, University Hospital 'San Giovanni di Dio e Ruggi D'Aragona', University of Salerno, Salerno, Italy., D'Antonio A; Department of Pathology, University Hospital 'San Giovanni di Dio e Ruggi D'Aragona', Salerno, Italy., Fiorentino F; Pathology Unit, S.M. delle Grazie Hospital, Pozzuoli, Italy., Facchini G; Medical Oncology Unit, S.M. delle Grazie Hospital, Pozzuoli, Italy., Lauro GD; Urology Unit, S.M. delle Grazie Hospital, Pozzuoli, Italy., Perdonà S; Department of Urogynecology, National Cancer Institute, Pascale Foundation (Scientific Institute for Research and Healthcare), Naples, Italy., Ventriglia J; Department of Urogynecology, National Cancer Institute, Pascale Foundation (Scientific Institute for Research and Healthcare), Naples, Italy., Aquino G; Pathology Unit, Istituto Nazionale Tumori Fondazione G. Pascale IRCCS, Naples, Italy., Feroce F; Pathology Unit, Istituto Nazionale Tumori Fondazione G. Pascale IRCCS, Naples, Italy., Borges Dos Reis R; Urology Division, Department of Surgery and Anatomy, Ribeirão Preto School Medicine, University of São Paulo, Ribeirão Preto, Brazil., Neder L; Department of Pathology and Forensic Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Brunelli M; Department of Pathology, University of Verona, Verona, Italy., Franco R; Pathology Unit, Department of Mental Health, Physic and Preventive Medicine University of Campania 'Luigi Vanvitelli', Naples, Italy., Zito Marino F; Pathology Unit, Department of Mental Health, Physic and Preventive Medicine University of Campania 'Luigi Vanvitelli', Naples, Italy.
Jazyk:	angličtina
Zdroj:	Frontiers in medicine [Front Med (Lausanne)] 2022 May 03; Vol. 9, pp. 874213. Date of Electronic Publication: 2022 May 03 (Print Publication: 2022).
DOI:	10.3389/fmed.2022.874213
Abstrakt:	Background: Penile cancer (PC) is an extremely rare malignancy, and the patients at advanced stages have currently limited treatment options with disappointing results. Immune checkpoint inhibitors anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) are currently changing the treatment of several tumors. Furthermore, the microsatellite instability (MSI) and the deficient mismatch repair system (dMMR) proteins represent predictive biomarkers for response to immune checkpoint therapy. Until present, few data have been reported related to PD-L1 expression and MSI in PC. The main aim of our study was the evaluation of PD-L1 expression in tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs) in immune cells and the analysis of dMMR/MSI status in a large series of PCs. Methods: A series of 72 PC, including 65 usual squamous cell carcinoma (USCC), 1 verrucous, 4 basaloid, 1 warty, and 1 mixed (warty-basaloid), was collected. Immunohistochemistry (IHC) was performed to assess PD-L1 expression using two different anti-PD-L1 antibodies (clone SP263 and SP142 Ventana) and MMR proteins expression using anti-MLH1, anti-PMS2, anti-MSH2, and anti-MSH6 antibodies. PCR analysis was performed for the detection of MSI status. Results: Of the 72 PC cases analyzed by IHC, 45 (62.5%) cases were TC positive and 57 (79%) cases were combined positive score (CPS) using PDL1 SP263. In our cohort, TILs were present in 62 out of 72 cases (86.1%), 47 (75.8%) out of 62 cases showed positivity to PDL1 clone SP142. In our series, 59 cases (82%) had pMMR, 12 cases (16.7%) had lo-paMMR, and only 1 case (1.3%) had MMR. PCR results showed that only one case lo-paMMR was MSI-H, and the case dMMR by IHC not confirmed MSI status. Conclusion: Our findings showed that PD-L1 expression and MSI status represent frequent biological events in this tumor suggesting a rationale for a new frontier in the treatment of patients with PC based on the immune checkpoint inhibitors. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor AM declared a shared affiliation with the authors FFe, GA at the time of review. (Copyright © 2022 Montella, Sabetta, Ronchi, De Sio, Arcaniolo, De Vita, Tirino, Caputo, D’Antonio, Fiorentino, Facchini, Lauro, Perdonà, Ventriglia, Aquino, Feroce, Borges Dos Reis, Neder, Brunelli, Franco and Zito Marino.)
Databáze:	MEDLINE
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