Sabina Davidsson1, Jessica Carlsson2, Francesca Giunchi3, Alyssa Harlow4, Peter Kirrander2, Jennifer Rider4, Michelangelo Fiorentino3, Ove Andrén2. 1. Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden. Electronic address: sabina.davidsson@regionorebrolan.se. 2. Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden. 3. Molecular Pathology Laboratory, Addarii Institute of Oncology, Department of Specialist Diagnostic and Experimental Medicine, University of Bologna, Bologna, Italy. 4. Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
Abstract
BACKGROUND: It has been hypothesized that PD-L1 expression in tumor cells and tumor-infiltrating immune (TII) cells may contribute to tumor progression by inhibiting antitumor immunity. OBJECTIVE: To investigate the association between PD-L1 expression in tumor cells and TII cells and clinical outcomes in penile cancer. DESIGN, SETTING, AND PARTICIPANTS: A cohort of 222 men treated for penile squamous cell carcinoma (SqCC) at Örebro University Hospital between 1984 and 2008 with long-term follow-up (median 34 mo) was evaluated for PD-L1 expression in tumor cells and TII cells via immunohistochemistry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Association between clinicopathological features and PD-L1 expression was estimated using χ2 and Fisher's exact tests. For survival analyses, Kaplan-Meier curves with log-rank tests and multivariate Cox proportional hazards regression models were used. RESULTS AND LIMITATIONS: We found that 32.1% of the tumors and 64.2% of the TII cells expressed PD-L1. Our data demonstrate that penile SqCC patients with PD-L1-positive tumor cells or TII cells are at significant risk of lower cancer-specific survival and that the prognostic value of PD-L1 expression was strongest for tumor cell positivity. The use of tissue microarrays rather than whole sections may be viewed as a limitation. CONCLUSIONS: Tumor PD-L1 expression independently identifies penile SqCC patients at risk of poor clinical outcomes. PATIENT SUMMARY: We investigated how many patients with penile cancer had tumors that manufactured PD-L1, a protein that decreases the ability of the immune system to fight cancer. We found that up to one-third of penile tumors make this protein. Patients whose tumors make PD-L1 have more aggressive penile cancer and worse clinical outcomes.
BACKGROUND: It has been hypothesized that PD-L1 expression in tumor cells and tumor-infiltrating immune (TII) cells may contribute to tumor progression by inhibiting antitumor immunity. OBJECTIVE: To investigate the association between PD-L1 expression in tumor cells and TII cells and clinical outcomes in penile cancer. DESIGN, SETTING, AND PARTICIPANTS: A cohort of 222 men treated for penile squamous cell carcinoma (SqCC) at Örebro University Hospital between 1984 and 2008 with long-term follow-up (median 34 mo) was evaluated for PD-L1 expression in tumor cells and TII cells via immunohistochemistry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Association between clinicopathological features and PD-L1 expression was estimated using χ2 and Fisher's exact tests. For survival analyses, Kaplan-Meier curves with log-rank tests and multivariate Cox proportional hazards regression models were used. RESULTS AND LIMITATIONS: We found that 32.1% of the tumors and 64.2% of the TII cells expressed PD-L1. Our data demonstrate that penile SqCC patients with PD-L1-positive tumor cells or TII cells are at significant risk of lower cancer-specific survival and that the prognostic value of PD-L1 expression was strongest for tumor cell positivity. The use of tissue microarrays rather than whole sections may be viewed as a limitation. CONCLUSIONS:TumorPD-L1 expression independently identifies penile SqCC patients at risk of poor clinical outcomes. PATIENT SUMMARY: We investigated how many patients with penile cancer had tumors that manufactured PD-L1, a protein that decreases the ability of the immune system to fight cancer. We found that up to one-third of penile tumors make this protein. Patients whose tumors make PD-L1 have more aggressive penile cancer and worse clinical outcomes.
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