Frequent PD-L1 expression in primary and metastatic penile squamous cell carcinoma: potential opportunities for immunotherapeutic approaches
A partir d'échantillons tumoraux prélevés sur 37 patients atteints d'un carcinome épidermoïde du pénis, cette étude met en évidence une fréquente surexpression de PD-L1
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 performed on whole tumor sections from thirty-seven 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 thirty-seven 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.
Annals of Oncology , résumé, 2016