Immune-checkpoint status in penile squamous cell carcinoma: a North American cohort

Autor: Rajni Sharma, Arthur L. Burnett, Diana Taheri, Mark W. Ball, George J. Netto, Margaret Cocks, Bernardo F.P. Ricardo, Stephania M. Bezerra, Alan K. Meeker, Alcides Chaux, Maria Del Carmen Rodriguez, Trinity J. Bivalacqua
Rok vydání: 2017
Předmět:
Adult
Male
0301 basic medicine
Pathology
medicine.medical_specialty
Stromal cell
Biopsy
Kaplan-Meier Estimate
CD8-Positive T-Lymphocytes
Biology
B7-H1 Antigen
Pathology and Forensic Medicine
Surgical pathology
03 medical and health sciences
Lymphocytes
Tumor-Infiltrating
0302 clinical medicine
PD-L1
Biomarkers
Tumor
Tumor Microenvironment
medicine
Humans
Penile cancer
Neoplasm Invasiveness
Penile Neoplasms
Aged
Neoplasm Staging
Proportional Hazards Models
Retrospective Studies
Aged
80 and over
Tissue microarray
FOXP3
Forkhead Transcription Factors
Middle Aged
medicine.disease
Immunohistochemistry
Immune checkpoint
030104 developmental biology
Tissue Array Analysis
Lymphatic Metastasis
030220 oncology & carcinogenesis
Baltimore
Carcinoma
Squamous Cell
biology.protein
Neoplasm Grading
Stromal Cells
Zdroj: Human Pathology. 59:55-61
ISSN: 0046-8177
DOI: 10.1016/j.humpath.2016.09.003
Popis: 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.
Databáze: OpenAIRE
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