What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 2: Clinic-Pathologic Correlations

doi:10.3390/cells10113165

. 2021 Nov 14;10(11):3165.

doi: 10.3390/cells10113165.

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 2: Clinic-Pathologic Correlations

Andrea Palicelli¹, Martina Bonacini², Stefania Croci², Cristina Magi-Galluzzi³, Sofia Cañete-Portillo³, Alcides Chaux⁴, Alessandra Bisagni¹, Eleonora Zanetti¹, Dario De Biase⁵, Beatrice Melli^{6

7}, Francesca Sanguedolce⁸, Magda Zanelli¹, Maria Paola Bonasoni¹, Loredana De Marco¹, Alessandra Soriano^{9

10}, Stefano Ascani^{11

12}, Maurizio Zizzo¹³, Carolina Castro Ruiz^{7

13}, Antonio De Leo¹⁴, Guido Giordano¹⁵, Matteo Landriscina¹⁵, Giuseppe Carrieri¹⁶, Luigi Cormio¹⁶, Daniel M Berney¹⁷, Jatin Gandhi¹⁸, Giacomo Santandrea^{1

7}, Maria Carolina Gelli¹, Alessandro Tafuni^{1

19}, Moira Ragazzi¹

Affiliations

¹ Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.
² Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.
³ Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
⁴ Department of Scientific Research, School of Postgraduate Studies, Norte University, Asunción 1614, Paraguay.
⁵ Department of Pharmacy and Biotechnology (FABIT), University of Bologna, 40126 Bologna, Italy.
⁶ Fertility Center, Department of Obstetrics and Gynecology, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.
⁷ Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41121 Modena, Italy.
⁸ Pathology Unit, Policlinico Riuniti, University of Foggia, 71122 Foggia, Italy.
⁹ Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
¹⁰ Gastroenterology Division, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.
¹¹ Pathology Unit, Azienda Ospedaliera Santa Maria di Terni, University of Perugia, 05100 Terni, Italy.
¹² Haematopathology Unit, CREO, Azienda Ospedaliera di Perugia, University of Perugia, 06129 Perugia, Italy.
¹³ Surgical Oncology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.
¹⁴ Molecular Diagnostic Unit, Azienda USL Bologna, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy.
¹⁵ Medical Oncology Unit, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy.
¹⁶ Department of Urology and Renal Transplantation, University of Foggia, 71122 Foggia, Italy.
¹⁷ Barts Cancer Institute, Queen Mary University of London, London EC1M 5PZ, UK.
¹⁸ Department of Pathology and Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.
¹⁹ Pathology Unit, Department of Medicine and Surgery, University of Parma, 43121 Parma, Italy.

PMID: 34831388
PMCID: PMC8618408
DOI: 10.3390/cells10113165

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 2: Clinic-Pathologic Correlations

Andrea Palicelli et al. Cells. 2021.

. 2021 Nov 14;10(11):3165.

doi: 10.3390/cells10113165.

Authors

Affiliations

¹ Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.
² Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.
³ Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
⁴ Department of Scientific Research, School of Postgraduate Studies, Norte University, Asunción 1614, Paraguay.
⁵ Department of Pharmacy and Biotechnology (FABIT), University of Bologna, 40126 Bologna, Italy.
⁶ Fertility Center, Department of Obstetrics and Gynecology, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.
⁷ Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41121 Modena, Italy.
⁸ Pathology Unit, Policlinico Riuniti, University of Foggia, 71122 Foggia, Italy.
⁹ Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
¹⁰ Gastroenterology Division, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.
¹¹ Pathology Unit, Azienda Ospedaliera Santa Maria di Terni, University of Perugia, 05100 Terni, Italy.
¹² Haematopathology Unit, CREO, Azienda Ospedaliera di Perugia, University of Perugia, 06129 Perugia, Italy.
¹³ Surgical Oncology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.
¹⁴ Molecular Diagnostic Unit, Azienda USL Bologna, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy.
¹⁵ Medical Oncology Unit, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy.
¹⁶ Department of Urology and Renal Transplantation, University of Foggia, 71122 Foggia, Italy.
¹⁷ Barts Cancer Institute, Queen Mary University of London, London EC1M 5PZ, UK.
¹⁸ Department of Pathology and Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.
¹⁹ Pathology Unit, Department of Medicine and Surgery, University of Parma, 43121 Parma, Italy.

PMID: 34831388
PMCID: PMC8618408
DOI: 10.3390/cells10113165

Abstract

Many studies have investigated the potential prognostic and predictive role of PD-L1 in prostatic carcinoma (PC). We performed a systematic literature review (PRISMA guidelines) to critically evaluate human tissue-based studies (immunohistochemistry, molecular analysis, etc.), experimental research (cell lines, mouse models), and clinical trials. Despite some controversial results and study limitations, PD-L1 expression by tumor cells may be related to clinic-pathologic features of adverse outcome, including advanced tumor stage (high pT, presence of lymph node, and distant metastases), positivity of surgical margins, high Grade Group, and castration resistance. Different PD-L1 positivity rates may be observed in matched primary PCs and various metastatic sites of the same patients. Over-fixation, type/duration of decalcification, and PD-L1 antibody clone may influence the immunohistochemical analysis of PD-L1 on bone metastases. PD-L1 seemed expressed more frequently by castration-resistant PCs (49%) as compared to hormone-sensitive PCs (17%). Some series found that PD-L1 positivity was associated with decreased time to castration resistance. Treatment with ipilimumab, cyclophosphamide/GVAX/degarelix, or degarelix alone may increase PD-L1 expression. Correlation of PD-L1 positivity with overall survival and outcomes related to tumor recurrence were rarely investigated; the few analyzed series produced conflicting results and sometimes showed limitations. Further studies are required. The testing and scoring of PD-L1 should be standardized.

Keywords: PD-L1; adenocarcinoma; cancer; checkpoint inhibitors; immunohistochemistry; immunotherapy; prostate; target-therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
PRISMA flowchart of our systematic literature review.

See this image and copyright information in PMC

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References

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[1] National Cancer Institute Surveillance, Epidemiology, and End Results Programs. [(accessed on 29 May 2021)]; Available online: https://seer.cancer.gov/statfacts/html/prost.html.

[2] National Cancer Institute Surveillance, Epidemiology, and End Results Programs. [(accessed on 29 May 2021)]; Available online: https://seer.cancer.gov/statfacts/html/prost.html.

[3] Falzarano S.M., Ferro M., Bollito E., Klein E.A., Carrieri G., Magi-Galluzzi C. Novel biomarkers and genomic tests in prostate cancer: A critical analysis. Ital. J. Urol. Nephrol. 2015;67:211–231. - PubMed

[4] Falzarano S.M., Ferro M., Bollito E., Klein E.A., Carrieri G., Magi-Galluzzi C. Novel biomarkers and genomic tests in prostate cancer: A critical analysis. Ital. J. Urol. Nephrol. 2015;67:211–231. - PubMed

[5] Tomlins S.A., Alshalalfa M., Davicioni E., Erho N., Yousefi K., Zhao S., Haddad Z., Den R.B., Dicker A.P., Trock B.J., et al. Characterization of 1577 primary prostate cancers reveals novel biological and clinicopathologic insights into molecular subtypes. Eur. Urol. 2015;68:555–567. doi: 10.1016/j.eururo.2015.04.033. - DOI - PMC - PubMed

[6] Tomlins S.A., Alshalalfa M., Davicioni E., Erho N., Yousefi K., Zhao S., Haddad Z., Den R.B., Dicker A.P., Trock B.J., et al. Characterization of 1577 primary prostate cancers reveals novel biological and clinicopathologic insights into molecular subtypes. Eur. Urol. 2015;68:555–567. doi: 10.1016/j.eururo.2015.04.033. - DOI - PMC - PubMed

[7] National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Prostate Cancer. Version 2.2021—17 February 2021. [(accessed on 29 May 2021)]. Available online: https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf.

[8] National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Prostate Cancer. Version 2.2021—17 February 2021. [(accessed on 29 May 2021)]. Available online: https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf.

[9] Santandrea G., Piana S., Valli R., Zanelli M., Gasparini E., De Leo A., Mandato V.D., Palicelli A. Immunohistochemical Biomarkers as a Surrogate of Molecular Analysis in Ovarian Carcinomas: A Review of the Literature. Diagnostics. 2021;11:199. doi: 10.3390/diagnostics11020199. - DOI - PMC - PubMed

[10] Santandrea G., Piana S., Valli R., Zanelli M., Gasparini E., De Leo A., Mandato V.D., Palicelli A. Immunohistochemical Biomarkers as a Surrogate of Molecular Analysis in Ovarian Carcinomas: A Review of the Literature. Diagnostics. 2021;11:199. doi: 10.3390/diagnostics11020199. - DOI - PMC - PubMed

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What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 2: Clinic-Pathologic Correlations

Affiliations

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 2: Clinic-Pathologic Correlations

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