Immunotherapy in Penile Squamous Cell Carcinoma: Present or Future? Multi-Target Analysis of Programmed Cell Death Ligand 1 Expression and Microsatellite Instability
BackgroundPenile 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 tr...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-05-01
|
| Series: | Frontiers in Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.874213/full |
| _version_ | 1828527577420005376 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Marco Montella |
| collection | DOAJ |
| description | BackgroundPenile 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.MethodsA 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.ResultsOf 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.ConclusionOur 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. |
| first_indexed | 2024-12-11T21:40:23Z |
| format | Article |
| id | doaj.art-9a6a8d4499bd476d94242632c581b84d |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-11T21:40:23Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-9a6a8d4499bd476d94242632c581b84d2022-12-22T00:49:52ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-05-01910.3389/fmed.2022.874213874213Immunotherapy in Penile Squamous Cell Carcinoma: Present or Future? Multi-Target Analysis of Programmed Cell Death Ligand 1 Expression and Microsatellite InstabilityMarco Montella0Rosalaura Sabetta1Andrea Ronchi2Marco De Sio3Davide Arcaniolo4Ferdinando De Vita5Giuseppe Tirino6Alessandro Caputo7Antonio D’Antonio8Francesco Fiorentino9Gaetano Facchini10Giovanni Di Lauro11Sisto Perdonà12Jole Ventriglia13Gabriella Aquino14Florinda Feroce15Rodolfo Borges Dos Reis16Luciano Neder17Matteo Brunelli18Renato Franco19Federica Zito Marino20Pathology Unit, Department of Mental Health, Physic and Preventive Medicine University of Campania “Luigi Vanvitelli”, Naples, ItalyPathology Unit, Department of Mental Health, Physic and Preventive Medicine University of Campania “Luigi Vanvitelli”, Naples, ItalyPathology Unit, Department of Mental Health, Physic and Preventive Medicine University of Campania “Luigi Vanvitelli”, Naples, ItalyUrology Unit, Department of Woman Child and of General and Specialist Surgery, University of Campania “Luigi Vanvitelli”, Naples, ItalyUrology Unit, Department of Woman Child and of General and Specialist Surgery, University of Campania “Luigi Vanvitelli”, Naples, ItalyOncology Unit, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples, ItalyOncology Unit, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples, ItalyDepartment of Medicine and Surgery, University Hospital “San Giovanni di Dio e Ruggi D’Aragona”, University of Salerno, Salerno, ItalyDepartment of Pathology, University Hospital “San Giovanni di Dio e Ruggi D’Aragona”, Salerno, ItalyPathology Unit, S.M. delle Grazie Hospital, Pozzuoli, ItalyMedical Oncology Unit, S.M. delle Grazie Hospital, Pozzuoli, ItalyUrology Unit, S.M. delle Grazie Hospital, Pozzuoli, ItalyDepartment of Urogynecology, National Cancer Institute, Pascale Foundation (Scientific Institute for Research and Healthcare), Naples, ItalyDepartment of Urogynecology, National Cancer Institute, Pascale Foundation (Scientific Institute for Research and Healthcare), Naples, Italy0Pathology Unit, Istituto Nazionale Tumori Fondazione G. Pascale IRCCS, Naples, Italy0Pathology Unit, Istituto Nazionale Tumori Fondazione G. Pascale IRCCS, Naples, Italy1Urology Division, Department of Surgery and Anatomy, Ribeirão Preto School Medicine, University of São Paulo, Ribeirão Preto, Brazil2Department of Pathology and Forensic Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil3Department of Pathology, University of Verona, Verona, ItalyPathology Unit, Department of Mental Health, Physic and Preventive Medicine University of Campania “Luigi Vanvitelli”, Naples, ItalyPathology Unit, Department of Mental Health, Physic and Preventive Medicine University of Campania “Luigi Vanvitelli”, Naples, ItalyBackgroundPenile 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.MethodsA 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.ResultsOf 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.ConclusionOur 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.https://www.frontiersin.org/articles/10.3389/fmed.2022.874213/fullpenile cancerpenile SCCPD-L1MSIHPVimmunotherapy |
| spellingShingle | 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 Immunotherapy in Penile Squamous Cell Carcinoma: Present or Future? Multi-Target Analysis of Programmed Cell Death Ligand 1 Expression and Microsatellite Instability Frontiers in Medicine penile cancer penile SCC PD-L1 MSI HPV immunotherapy |
| title | Immunotherapy in Penile Squamous Cell Carcinoma: Present or Future? Multi-Target Analysis of Programmed Cell Death Ligand 1 Expression and Microsatellite Instability |
| title_full | Immunotherapy in Penile Squamous Cell Carcinoma: Present or Future? Multi-Target Analysis of Programmed Cell Death Ligand 1 Expression and Microsatellite Instability |
| title_fullStr | Immunotherapy in Penile Squamous Cell Carcinoma: Present or Future? Multi-Target Analysis of Programmed Cell Death Ligand 1 Expression and Microsatellite Instability |
| title_full_unstemmed | Immunotherapy in Penile Squamous Cell Carcinoma: Present or Future? Multi-Target Analysis of Programmed Cell Death Ligand 1 Expression and Microsatellite Instability |
| title_short | Immunotherapy in Penile Squamous Cell Carcinoma: Present or Future? Multi-Target Analysis of Programmed Cell Death Ligand 1 Expression and Microsatellite Instability |
| title_sort | immunotherapy in penile squamous cell carcinoma present or future multi target analysis of programmed cell death ligand 1 expression and microsatellite instability |
| topic | penile cancer penile SCC PD-L1 MSI HPV immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.874213/full |
| work_keys_str_mv | AT marcomontella immunotherapyinpenilesquamouscellcarcinomapresentorfuturemultitargetanalysisofprogrammedcelldeathligand1expressionandmicrosatelliteinstability AT rosalaurasabetta immunotherapyinpenilesquamouscellcarcinomapresentorfuturemultitargetanalysisofprogrammedcelldeathligand1expressionandmicrosatelliteinstability AT andrearonchi immunotherapyinpenilesquamouscellcarcinomapresentorfuturemultitargetanalysisofprogrammedcelldeathligand1expressionandmicrosatelliteinstability AT marcodesio immunotherapyinpenilesquamouscellcarcinomapresentorfuturemultitargetanalysisofprogrammedcelldeathligand1expressionandmicrosatelliteinstability AT davidearcaniolo immunotherapyinpenilesquamouscellcarcinomapresentorfuturemultitargetanalysisofprogrammedcelldeathligand1expressionandmicrosatelliteinstability AT ferdinandodevita immunotherapyinpenilesquamouscellcarcinomapresentorfuturemultitargetanalysisofprogrammedcelldeathligand1expressionandmicrosatelliteinstability AT giuseppetirino immunotherapyinpenilesquamouscellcarcinomapresentorfuturemultitargetanalysisofprogrammedcelldeathligand1expressionandmicrosatelliteinstability AT alessandrocaputo immunotherapyinpenilesquamouscellcarcinomapresentorfuturemultitargetanalysisofprogrammedcelldeathligand1expressionandmicrosatelliteinstability AT antoniodantonio immunotherapyinpenilesquamouscellcarcinomapresentorfuturemultitargetanalysisofprogrammedcelldeathligand1expressionandmicrosatelliteinstability AT francescofiorentino immunotherapyinpenilesquamouscellcarcinomapresentorfuturemultitargetanalysisofprogrammedcelldeathligand1expressionandmicrosatelliteinstability AT gaetanofacchini immunotherapyinpenilesquamouscellcarcinomapresentorfuturemultitargetanalysisofprogrammedcelldeathligand1expressionandmicrosatelliteinstability AT giovannidilauro immunotherapyinpenilesquamouscellcarcinomapresentorfuturemultitargetanalysisofprogrammedcelldeathligand1expressionandmicrosatelliteinstability AT sistoperdona immunotherapyinpenilesquamouscellcarcinomapresentorfuturemultitargetanalysisofprogrammedcelldeathligand1expressionandmicrosatelliteinstability AT joleventriglia immunotherapyinpenilesquamouscellcarcinomapresentorfuturemultitargetanalysisofprogrammedcelldeathligand1expressionandmicrosatelliteinstability AT gabriellaaquino immunotherapyinpenilesquamouscellcarcinomapresentorfuturemultitargetanalysisofprogrammedcelldeathligand1expressionandmicrosatelliteinstability AT florindaferoce immunotherapyinpenilesquamouscellcarcinomapresentorfuturemultitargetanalysisofprogrammedcelldeathligand1expressionandmicrosatelliteinstability AT rodolfoborgesdosreis immunotherapyinpenilesquamouscellcarcinomapresentorfuturemultitargetanalysisofprogrammedcelldeathligand1expressionandmicrosatelliteinstability AT lucianoneder immunotherapyinpenilesquamouscellcarcinomapresentorfuturemultitargetanalysisofprogrammedcelldeathligand1expressionandmicrosatelliteinstability AT matteobrunelli immunotherapyinpenilesquamouscellcarcinomapresentorfuturemultitargetanalysisofprogrammedcelldeathligand1expressionandmicrosatelliteinstability AT renatofranco immunotherapyinpenilesquamouscellcarcinomapresentorfuturemultitargetanalysisofprogrammedcelldeathligand1expressionandmicrosatelliteinstability AT federicazitomarino immunotherapyinpenilesquamouscellcarcinomapresentorfuturemultitargetanalysisofprogrammedcelldeathligand1expressionandmicrosatelliteinstability |