Immune-checkpoint status in penile squamous cell carcinoma: a North American cohort.
Penile squamous cell carcinoma (SCC) is primarily treated by surgical resection. Locally advanced and metastatic diseases 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. Tissue microarrays were stained with immunohistochemistry for PD-L1, FOXP3, CD8, and Ki-67. PD-L1 was investigated using rabbit monoclonal anti-PD-L1 antibody (Cell Signaling, Boston, MA; E1L3N, 1:100). Overall, 21 (40%) of 53 penile SCCs had positive PD-L1 expression. PD-L1 was expressed by a significant proportion of advanced penile SCC. Forty-four percent (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 (49%) of 53 cases. FOXP3 expression in stromal immune cells correlated with tumor thickness (P = .0086). The ratio of CD8/FOXP3 was greater than 1 in 62% of cases in tumor-infiltrating immune cells and 34% of cases in stromal immune cells. 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.
Departments of Pathology, Urology, and Oncology, The Johns Hopkins Hospital, Baltimore, MD, 21231.
Margaret
M
Cocks
Departments of Pathology, Urology, and Oncology, The Johns Hopkins Hospital, Baltimore, MD, 21231; Department of Pathology, Isfahan Kidney Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran, 81746-73461.
Diana
D
Taheri
Departments of Pathology, Urology, and Oncology, The Johns Hopkins Hospital, Baltimore, MD, 21231.
Mark W
MW
Ball
Departments of Pathology, Urology, and Oncology, The Johns Hopkins Hospital, Baltimore, MD, 21231.
Stephania M
SM
Bezerra
Departments of Pathology, Urology, and Oncology, The Johns Hopkins Hospital, Baltimore, MD, 21231.
Maria
M
Del Carmen Rodriguez
Departments of Pathology, Urology, and Oncology, The Johns Hopkins Hospital, Baltimore, MD, 21231.
Bernardo F P
BFP
Ricardo
Departments of Pathology, Urology, and Oncology, The Johns Hopkins Hospital, Baltimore, MD, 21231.
Trinity J
TJ
Bivalacqua
Departments of Pathology, Urology, and Oncology, The Johns Hopkins Hospital, Baltimore, MD, 21231.
Rajni B
RB
Sharma
Departments of Pathology, Urology, and Oncology, The Johns Hopkins Hospital, Baltimore, MD, 21231.
Alan
A
Meeker
Department of Scientific Research, Norte University, Asunción 1614, Paraguay.
Alcides
A
Chaux
Departments of Pathology, Urology, and Oncology, The Johns Hopkins Hospital, Baltimore, MD, 21231.
Arthur L
AL
Burnett
Departments of Pathology, Urology, and Oncology, The Johns Hopkins Hospital, Baltimore, MD, 21231. Electronic address: Gnetto@uabmc.edu.
George J
GJ
Netto
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000032:analysis*; D015142:Baltimore; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D051858:Forkhead Transcription Factors / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010412:Penile Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D017154:Stromal Cells / Q000276:immunology / Q000473:pathology; D046888:Tissue Array Analysis; D059016:Tumor Microenvironment
D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
CD8; FOXP3; Immune checkpoint; PD-L1; Penile cancer; Squamous cell carcinoma