Frequent PD-L1 expression in primary and metastatic penile squamous cell carcinoma: potential opportunities for immunotherapeutic approaches

Abstract

Background: 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.

Patients and methods: 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.

Results: 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).

Conclusions: 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.

Keywords: PD-L1; immunohistochemistry; immunotherapy; penile cancer; squamous cell carcinoma.

Figure 1.

Positive PD-L1 expression in primary penile squamous cell carcinoma tumors. (B, D, and F) PD-L1 IHC demonstrates frequent moderate to strong membranous staining in primary penile squamous cell carcinoma, including well differentiated (A and B), moderately differentiated (C and D), and poorly differentiated (E and F) tumors. Magnification, ×20.

Figure 2.

Negative PD-L1 expression in primary penile squamous cell carcinoma tumors. (B, D, and F) PD-L1 IHC is negative in a subset of primary penile squamous cell carcinoma, including well differentiated (A and B), moderately differentiated (C and D), and poorly differentiated (E and F) tumors. Magnification, ×20.

Figure 3.

Concordant PD-L1 expression in matched primary and metastatic penile squamous cell carcinoma tumors. PD-L1 IHC (right panels) in matched primary and metastatic penile squamous cell carcinoma from two patients. For patient A, both the primary and metastatic tumor show high positive PD-L1 expression, while for patient B, both the primary and metastatic tumor show low positive PD-L1 expression. The percentage of cells with membranous staining shows strong positive correlation (ρ = 0.72; 0.032 < P < 0.036) between matched primary and metastatic penile squamous cell carcinoma tumors. Magnification, ×20.