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Immune-checkpoint status in penile squamous cell carcinoma: a North American cohort.
Hum Pathol. 2017 01; 59:55-61.HP

Abstract

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.

Authors+Show Affiliations

Departments of Pathology, Urology, and Oncology, The Johns Hopkins Hospital, Baltimore, MD, 21231.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.Departments of Pathology, Urology, and Oncology, The Johns Hopkins Hospital, Baltimore, MD, 21231.Departments of Pathology, Urology, and Oncology, The Johns Hopkins Hospital, Baltimore, MD, 21231.Departments of Pathology, Urology, and Oncology, The Johns Hopkins Hospital, Baltimore, MD, 21231.Departments of Pathology, Urology, and Oncology, The Johns Hopkins Hospital, Baltimore, MD, 21231.Departments of Pathology, Urology, and Oncology, The Johns Hopkins Hospital, Baltimore, MD, 21231.Departments of Pathology, Urology, and Oncology, The Johns Hopkins Hospital, Baltimore, MD, 21231.Departments of Pathology, Urology, and Oncology, The Johns Hopkins Hospital, Baltimore, MD, 21231.Department of Scientific Research, Norte University, Asunción 1614, Paraguay.Departments of Pathology, Urology, and Oncology, The Johns Hopkins Hospital, Baltimore, MD, 21231.Departments of Pathology, Urology, and Oncology, The Johns Hopkins Hospital, Baltimore, MD, 21231. Electronic address: Gnetto@uabmc.edu.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27663086

Citation

Cocks, Margaret, et al. "Immune-checkpoint Status in Penile Squamous Cell Carcinoma: a North American Cohort." Human Pathology, vol. 59, 2017, pp. 55-61.
Cocks M, Taheri D, Ball MW, et al. Immune-checkpoint status in penile squamous cell carcinoma: a North American cohort. Hum Pathol. 2017;59:55-61.
Cocks, M., Taheri, D., Ball, M. W., Bezerra, S. M., Del Carmen Rodriguez, M., Ricardo, B. F. P., Bivalacqua, T. J., Sharma, R. B., Meeker, A., Chaux, A., Burnett, A. L., & Netto, G. J. (2017). Immune-checkpoint status in penile squamous cell carcinoma: a North American cohort. Human Pathology, 59, 55-61. https://doi.org/10.1016/j.humpath.2016.09.003
Cocks M, et al. Immune-checkpoint Status in Penile Squamous Cell Carcinoma: a North American Cohort. Hum Pathol. 2017;59:55-61. PubMed PMID: 27663086.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immune-checkpoint status in penile squamous cell carcinoma: a North American cohort. AU - Cocks,Margaret, AU - Taheri,Diana, AU - Ball,Mark W, AU - Bezerra,Stephania M, AU - Del Carmen Rodriguez,Maria, AU - Ricardo,Bernardo F P, AU - Bivalacqua,Trinity J, AU - Sharma,Rajni B, AU - Meeker,Alan, AU - Chaux,Alcides, AU - Burnett,Arthur L, AU - Netto,George J, Y1 - 2016/09/20/ PY - 2016/07/06/received PY - 2016/08/29/revised PY - 2016/09/01/accepted PY - 2016/9/25/pubmed PY - 2017/8/29/medline PY - 2016/9/25/entrez KW - CD8 KW - FOXP3 KW - Immune checkpoint KW - PD-L1 KW - Penile cancer KW - Squamous cell carcinoma SP - 55 EP - 61 JF - Human pathology JO - Hum. Pathol. VL - 59 N2 - 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. SN - 1532-8392 UR - https://www.unboundmedicine.com/medline/citation/27663086/Immune_checkpoint_status_in_penile_squamous_cell_carcinoma:_a_North_American_cohort_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0046-8177(16)30211-8 DB - PRIME DP - Unbound Medicine ER -