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.
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.
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.
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.
Frontiers in medicine. 2022 May 03*** epublish ***
Marco Montella, Rosalaura Sabetta, Andrea Ronchi, Marco De Sio, Davide Arcaniolo, Ferdinando De Vita, Giuseppe Tirino, Alessandro Caputo, Antonio D'Antonio, Francesco Fiorentino, Gaetano Facchini, Giovanni Di Lauro, Sisto Perdonà, Jole Ventriglia, Gabriella Aquino, Florinda Feroce, Rodolfo Borges Dos Reis, Luciano Neder, Matteo Brunelli, Renato Franco, Federica Zito Marino
Pathology Unit, Department of Mental Health, Physic and Preventive Medicine University of Campania "Luigi Vanvitelli", Naples, Italy., Urology Unit, Department of Woman Child and of General and Specialist Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy., Oncology Unit, Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy., Department of Medicine and Surgery, University Hospital "San Giovanni di Dio e Ruggi D'Aragona", University of Salerno, Salerno, Italy., Department of Pathology, University Hospital "San Giovanni di Dio e Ruggi D'Aragona", Salerno, Italy., Pathology Unit, S.M. delle Grazie Hospital, Pozzuoli, Italy., Medical Oncology Unit, S.M. delle Grazie Hospital, Pozzuoli, Italy., Urology Unit, S.M. delle Grazie Hospital, Pozzuoli, Italy., Department of Urogynecology, National Cancer Institute, Pascale Foundation (Scientific Institute for Research and Healthcare), Naples, Italy., Pathology Unit, Istituto Nazionale Tumori Fondazione G. Pascale IRCCS, Naples, Italy., Urology Division, Department of Surgery and Anatomy, Ribeirão Preto School Medicine, University of São Paulo, Ribeirão Preto, Brazil., Department of Pathology and Forensic Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Department of Pathology, University of Verona, Verona, Italy.