Assessment of PD-L1, TROP2, and nectin-4 expression in penile squamous cell carcinoma

Tekin, Burak; Cheville, John C.; Herrera Hernandez, Loren; Negron, Vivian; Smith, Carin Y.; Jenkins, Sarah M.; Dasari, Surendra; Enninga, Elizabeth Ann L.; Norgan, Andrew P.; Menon, Santosh; Cubilla, Antonio L.; Whaley, Rumeal D.; Jimenez, Rafael E.; Thompson, R. Houston; Leibovich, Bradley C.; Karnes, R. Jeffrey; Boorjian, Stephen A.; Pagliaro, Lance C.; Erickson, Lori A.; Guo, Ruifeng; Gupta, Sounak

doi:10.1016/j.humpath.2023.10.003

Cited by 13 publications

(2 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Certain mutations, including those in TP53, FAT1, CASP8, and FBXW7, are more common in HPV-negative than HPV-positive PSCC [7,10]. Programmed death-ligand-1 (PD-L1) immunohistochemistry is positive in 33-60% of both HPV-related and -unrelated tumors [7,[14][15][16]. High tumor mutational burden (TMB) is seen in 18-20% of cases, with one study finding TMB of at least 10 mutations per Mb in 30.8% of HPV-related tumors, but not in HPV-unrelated tumors [7,9].…”

Section: Molecular Profilementioning

confidence: 99%

“…It targets cells with expression of the cell surface protein TROP-2. Tekin et al conducted a study of TROP-2, nectin-4, and PD-L1 expression in PSCC primary tumor samples [ 14 ]. Using archived specimens (N = 121) from total or partial penectomies, immunohistochemistry was performed to determine H-score (range, 0 to 300), then expression was classified as low, intermediate, or high for TROP-2 and nectin-4, and positive or negative for PD-L1.…”

Section: Antibody-drug Conjugatesmentioning

confidence: 99%

See 1 more Smart Citation

Therapeutic Targets in Advanced Penile Cancer: From Bench to Bedside

Pagliaro,

Tekin,

Gupta

et al. 2024

Cancers

Self Cite

View full text Add to dashboard Cite

Discovery of effective systemic therapies for patients with advanced penile cancer has been slow to occur. Comprehensive genomic profiling from several studies shed light on the molecular oncogenesis of penile squamous cell carcinoma (PSCC) and differences between HPV-related and unrelated tumors. While these two subsets of PSCC appear distinct in their biology, there are not yet specific treatment strategies recommended on that basis. Cell surface proteins have been identified that may potentially serve as drug targets for monoclonal antibodies or small molecule inhibitors. Here, we review some of the new biological insights regarding PSCC that could lead to improved therapies, as well as the related clinical trials recently completed or in progress. We conclude that antibody-drug conjugates are especially promising, as are the combinations of immune checkpoint inhibitors with other types of drugs.

show abstract

Section: Molecular Profilementioning

confidence: 99%

Section: Antibody-drug Conjugatesmentioning

confidence: 99%

Therapeutic Targets in Advanced Penile Cancer: From Bench to Bedside

Pagliaro,

Tekin,

Gupta

et al. 2024

Cancers

Self Cite

View full text Add to dashboard Cite

show abstract

Nectin‐4 Expression in Prostatic Adenocarcinoma: An Immunohistochemical Study

Baraban,

Vlachou,

Patel

et al. 2025

The Prostate

View full text Add to dashboard Cite

BackgroundThe Nectin‐4 directed antibody drug conjugate enfortumab vedotin (EV) has emerged as frontline systemic therapy in combination with immune checkpoint blockade for urothelial carcinoma (UC), capitalizing on the ubiquitous expression of this protein in UC. There is limited data available regarding expression of Nectin‐4 by immunohistochemistry in prostate cancer, but this is of interest as a substantial number of UC patients likely to receive EV have concomitant prostate cancer.MethodsNectin‐4 protein expression was evaluated by immunohistochemistry in tissue microarrays encompassing a cohort of 302 prostatic adenocarcinomas spanning Grade Groups 1–5. Intensity of expression was scored from 1 (weak) to 3 (intense staining readily apparent at low magnification). H‐scores were calculated by multiplying the percentage of cells staining by the intensity of expression.ResultsNectin‐4 expression was frequently observed in benign prostate tissue (86% of cases, mean H‐score of 40, median 20, interquartile range [IQR]: 10–60) and in prostatic adenocarcinoma (91% of cases, mean H‐score of 90, median 70, IQR: 20–150). Significant differences in Nectin‐4 expression among prostatic adenocarcinoma Grade Groups 1–5 were not observed. Across all prostatic adenocarcinomas evaluated, the mean Nectin‐4 H‐score of 90 was statistically significantly higher than the mean H‐score of 40 observed in benign prostate tissue (p < 0.001). Three of four prostatic ductal adenocarcinomas showed Nectin‐4 expression, with a median H‐score of 250 (IQR: 152–300).ConclusionsNectin‐4 protein expression is common in benign prostate tissue and prostatic adenocarcinoma. These findings provide a rationale for future studies investigating potential activity of EV in prostate cancer.

show abstract