Despite aggressive multimodal therapy, locally advanced and/or metastatic penile squamous cell carcinoma (SqCC) is associated with significant morbidity and mortality, indicating a need for new therapeutic options. Given the emerging clinical utility of immunotherapeutics, we sought to assess the incidence and potential clinical significance of PD-L1 expression in penile SqCC.
Using an anti-PD-L1 primary antibody (clone 5H1), immunohistochemistry was carried out on whole tumor sections from 37 patients with penile SqCC treated at our institution between 2005 and 2013. PD-L1-positive tumors were defined as those with membranous staining in ≥5% of tumor cells. Association between PD-L1 expression and clinicopathologic parameters was examined using Fisher's exact test. Correlation between PD-L1 expression in primary tumors and matched metastases was assessed using the Spearman rank correlation coefficient (ρ). The difference in cancer-specific mortality between PD-L1-positive and -negative groups was examined using the log-rank test.
Twenty-three (62.2%) of 37 primary tumors were positive for PD-L1 expression, and there was strong positive correlation of PD-L1 expression in primary and metastatic samples (ρ = 0.72; 0.032 < P < 0.036). Primary tumor PD-L1 expression was significantly associated with usual type histology (P = 0.040) and regional lymph node metastasis (P = 0.024), as well as decreased cancer-specific survival (P = 0.011).
The majority of primary penile SqCC tumors express PD-L1, which is associated with high-risk clinicopathologic features and poor clinical outcome. These data provide a rational basis for further investigation of anti-PD-1 and anti-PD-L1 immunotherapeutics in patients with advanced penile SqCC.
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2016 May 23 [Epub ahead of print]
A M Udager, T-Y Liu, S L Skala, M J Magers, A S McDaniel, D E Spratt, F Y Feng, J Siddiqui, X Cao, K L Fields, T M Morgan, G S Palapattu, A Z Weizer, A M Chinnaiyan, A Alva, J S Montgomery, S A Tomlins, H Jiang, R Mehra
Department of Pathology, University of Michigan Health System, Ann Arbor, USA., Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, USA., Department of Pathology, University of Michigan Health System, Ann Arbor, USA., Department of Pathology, University of Michigan Health System, Ann Arbor, USA., Department of Pathology, University of Michigan Health System, Ann Arbor, USA., Department of Radiation Oncology, University of Michigan Health System, Ann Arbor Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor., Department of Radiation Oncology, University of Michigan Health System, Ann Arbor Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor., Department of Urology, University of Michigan Health System, Ann Arbor, USA., Department of Urology, University of Michigan Health System, Ann Arbor, USA., Department of Pathology, University of Michigan Health System, Ann Arbor, USA., Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Health System, Ann Arbor, USA., Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Health System, Ann Arbor, USA., Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Health System, Ann Arbor, USA., Department of Pathology, University of Michigan Health System, Ann Arbor, USA Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor Department of Urology, University of Michigan Health System, Ann Arbor, USA Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Health System, Ann Arbor, USA Michigan Center for Translational Pathology, Ann Arbor, USA., Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor Howard Hughes Medical Institute, Ann Arbor, USA., Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Health System, Ann Arbor, USA., Department of Pathology, University of Michigan Health System, Ann Arbor, USA Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor Department of Urology, University of Michigan Health System, Ann Arbor, USA Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Health System, Ann Arbor, USA., Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, USA., Department of Pathology, University of Michigan Health System, Ann Arbor, USA Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor Department of Urology, University of Michigan Health System, Ann Arbor, USA .