Penile squamous cell carcinoma (SCC) is primarily treated by surgical resection. Locally advanced and metastatic disease require a multidisciplinary treatment approach. However, mortality and morbidity remain high and novel molecular and immunotherapeutic targets are actively being sought. We investigated the expression of immune checkpoint markers in penile cancers. Fifty-three invasive penile SCCs diagnosed between 1985 and 2013 were retrieved from our surgical pathology archives. Representative formalin-fixed, paraffin-embedded archival blocks were used for the construction of 2 high-density tissue microarrays (TMAs). TMAs were stained with immunohistochemistry (IHC) for PD-L1, FOXP3, CD8 and Ki-67. PD-L1 was investigated using rabbit monoclonal anti PD-L1 antibody (Cell Signaling, E1L3N, 1:100). Overall 21/53 (40%) of penile SCCs had positive PD-L1 expression. PD-L1 was expressed by a significant proportion of advanced penile SCC. 44% (15/34) of stage pT2 or more SCC and 38% (6/16) of tumors with lymph node metastasis were positive for PD-L1. PD-L1 expression did not correlate with patient age, tumor location, histologic subtype, tumor stage, anatomic depth of invasion or tumor grade. FOXP3 expression in tumoral immune cells was found in 26/53 (49%) of cases. FOXP3 expression in stromal immune cells correlated with tumor thickness (P=.0086). The ratio of CD8:FOXP3 was >1 in 62% of tumor-infiltrating immune cells and 34% of stromal immune cells samples. Our current study is the largest to assess expression of PD-L1 in a clinically well-annotated North American cohort of penile SCC. Our findings support a rationale for targeting immune-checkpoint inhibitor pathways in advanced penile SCC.
Human pathology. 2016 Sep 20 [Epub ahead of print]
Margaret Cocks, Diana Taheri, Mark W Ball, Stephania M Bezerra, Maria Del Carmen Rodriguez, Bernardo F P Ricardo, Trinity J Bivalacqua, Rajni B Sharma, Alan Meeker, Alcides Chaux, Arthur L Burnett, George J Netto
Departments of Pathology, Urology and Oncology, The Johns Hopkins Hospital, Baltimore, MD, USA., Departments of Pathology, Urology and Oncology, The Johns Hopkins Hospital, Baltimore, MD, USA; Isfahan University of Medical Sciences, Isfahan Kidney Diseases Research Center, Pathology, Isfahan, Iran., Department of Scientific Research, Norte University, Asunción, 1614, Paraguay.