What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review (Part 6): Correlation of PD-L1 Expression with the Status of Mismatch Repair System, BRCA, PTEN, and Other Genes

Biomedicines

Stefania Croci¹  Martina Bonacini¹  Jatin Gandhi²  Sofia Cañete-Portillo³  Dario De Biase⁴  Alcides Chaux⁵  Giuseppe Carrieri⁶  Luigi Cormio⁶  Beatrice Melli⁷  Guido Giordano⁸  Matteo Landriscina⁸  Davide Nicoli⁹  Enrico Farnetti⁹  Antonio De Leo^1,10  Stefano Ascani^1,11  Maria Paola Bonasoni^1,12  Alessandro Tafuni^1,12  Eleonora Zanetti^1,12  Simonetta Piana^1,12  Alessandra Bisagni^1,12  Magda Zanelli^1,12  Andrea Palicelli^1,12  Moira Ragazzi^1,12  Francesca Sanguedolce^1,13 

[1] Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy;Department of Pathology and Laboratory Medicine, University of Washington, Seattle, WA 98195, USA;Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA;Department of Pharmacy and Biotechnology (FABIT), University of Bologna, 40126 Bologna, Italy;Department of Scientific Research, School of Postgraduate Studies, Norte University, Asuncion 1614, Paraguay;Department of Urology and Renal Transplantation, University of Foggia, 71122 Foggia, Italy;Fertility Center, Department of Obstetrics and Gynecology, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy;Medical Oncology Unit, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy;Molecular Biology Laboratory, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy;Molecular Diagnostic Unit, Azienda USL Bologna, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy;Pathology Unit, Azienda Ospedaliera Santa Maria di Terni, University of Perugia, 05100 Terni, Italy;Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy;Pathology Unit, Policlinico Riuniti, University of Foggia, 71122 Foggia, Italy;

关键词: PD-L1;    prostate;    cancer;    BRCA;    mismatch repair;    microsatellite instability;   

DOI  :  10.3390/biomedicines10020236

来源: DOAJ

【 摘 要 】

Pembrolizumab (anti-PD-1) is allowed in selected metastatic castration-resistant prostate cancer (PC) patients showing microsatellite instability/mismatch repair system deficiency (MSI-H/dMMR). BRCA1/2 loss-of-function is linked to hereditary PCs and homologous recombination DNA-repair system deficiency: poly-ADP-ribose-polymerase inhibitors can be administered to BRCA-mutated PC patients. Recently, docetaxel-refractory metastatic castration-resistant PC patients with BRCA1/2 or ATM somatic mutations had higher response rates to pembrolizumab. PTEN regulates cell cycle/proliferation/apoptosis through pathways including the AKT/mTOR, which upregulates PD-L1 expression in PC. Our systematic literature review (PRISMA guidelines) investigated the potential correlations between PD-L1 and MMR/MSI/BRCA/PTEN statuses in PC, discussing few other relevant genes. Excluding selection biases, 74/677 (11%) PCs showed dMMR/MSI; 8/67 (12%) of dMMR/MSI cases were PD-L1+. dMMR-PCs included ductal (3%) and acinar (14%) PCs (all cases tested for MSI were acinar-PCs). In total, 15/39 (39%) PCs harbored BRCA1/2 aberrations: limited data are available for PD-L1 expression in these patients. 13/137 (10%) PTEN- PCs were PD-L1+; 10/29 (35%) PD-L1+ PCs showed PTEN negativity. SPOP mutations may increase PD-L1 levels, while the potential correlation between PD-L1 and ERG expression in PC should be clarified. Further research should verify how the efficacy of PD-1 inhibitors in metastatic castration-resistant PCs is related to dMMR/MSI, DNA-damage repair genes defects, or PD-L1 expression.

【 授权许可】

Unknown