Expression of Programmed Death Ligand 1 (PD-L1) in penile cancer is of prognostic value and associated with HPV status

PD-L1 inhibits T-cell function and prevents tumor eradication. This is facilitated by PD-L1(+) tumor cells and PD-L1(+) immune cells, and can be prevented by anti-PD-1/PD-L1 immunotherapy. In advanced penile cancer there is a need for new therapeutic strategies. This study investigated PD-L1 expression in penile cancers and compared PD-L1 expression with disease-specific survival, lymph-node metastases at diagnosis, and high-risk human papilloma virus (hrHPV) status in a large patient cohort.

213 primary tumors were immunohistochemically stained for PD-L1 and scored for tumor (percentage), stroma (binary) and PD-L1(+) tumor infiltrating macrophages (TIM). Additionally, PD-L1(+) tumors were scored for expression pattern: diffuse or predominantly present at tumor-stroma margin.

Staining was successful in 200 tumors. 75% were hrHPV(-). Median follow-up was 62 months. Of 200 tumors, 96 (48%) were PD-L1(+) (scored ≥1%), of which 59 (62%) had a marginal expression pattern and 79 (82%) were hrHPV(-) (p=0.03). Compared to PD-L1(-) tumors, the PD-L1 expression patterns each had different prognostic values, in the whole cohort as well as in the hrHPV(-) subgroup. In multivariable analyses, marginal expression pattern was associated with absence of lymph-node metastases (OR 0.4), while diffuse expression was associated with poor survival (HR 2.58). These results were more prominent in the hrHPV(-) subgroup (OR 0.25 and HR 3.92, respectively).

PD-L1 was expressed in 48% of penile carcinomas, and mainly in HPV(-) tumors. Pattern of expression was a prognostic factor as marginal expression was associated with absence of lymph-node metastases, and a diffuse expression with poor survival.

The Journal of urology. 2016 [Epub ahead of print]

Sarah R Ottenhof, Rosa S Djajadiningrat, Jeroen de Jong, Helene H Thygesen, Simon Horenblas, Ekaterina S Jordanova

Department of Urological Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands., Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands., Department of Biometrics, Netherlands Cancer Institute, Amsterdam, the Netherlands., Center Gynecological Oncology Amsterdam (CGOA), Department of Obstetrics and Gynecology VU University Medical Center, Amsterdam, the Netherlands.