Lobo, Anandi, Mishra, Sourav K, Jha, Shilpy, Tiwari, Ankit, Kapoor, Rahul, Sharma, Shivani, Kaushal, Seema, Kiranmai, N Sri, Das, M Rakshitha, Peddinti, Kamal P, Sharma, Shailendra K, Bhardwaj, Nitin, Arora, Samriti, Jain, Deepika, Jain, Ekta, Munjal, Gauri, Shinde, Sayali, Malik, Vipra, Singh, Hena, Varshney, Juhi, Pradhan, Dinesh, Dixit, Mallika, Pattnaik, Niharika, Sharma, Ashish K, Barapatre, Yogesh R, Pradhan, Manas, Satapathy, Kaliprasad, Rath, Debadarshi, Jaiswal, Sunil, Das, Stithi, Khadenga, Chiraranjan, Routa, Sudhasmita, Baisakh, Manas R, Tiwari, Romila, Sampat, Nakul Y, Chakrabarti, Indranil, Parwani, Anil V, Mohanty, Sambit K (January 2024) Evaluation of programmed cell death ligand 1 expression in a contemporary cohort of penile squamous cell carcinoma and its correlation with clinicopathologic and survival parameters: A study of 134 patients. American Journal of Clinical Pathology. aqad107. ISSN 0002-9173
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Abstract
OBJECTIVES: Penile squamous cell carcinomas (PCs) are rare malignancies with a dismal prognosis in a metastatic setting; therefore, novel immunotherapeutic modalities are an unmet need. One such modality is the immune checkpoint molecule programmed cell death ligand 1 (PD-L1). We sought to analyze PD-L1 expression and its correlation with various clinicopathologic parameters in a contemporary cohort of 134 patients with PC. METHODS: A cohort of 134 patients with PC was studied for PD-L1 immunohistochemistry. The PD-L1 expression was evaluated using a combined proportion score with a cutoff of 1 or higher to define positivity. The results were correlated with various clinicopathologic parameters. RESULTS: Overall, 77 (57%) patients had positive PD-L1 expression. Significantly high PD-L1 expression was observed in high-grade tumors (P = .006). We found that 37% of human papillomavirus (HPV)-associated subtypes and 73% of other histotype tumors expressed PD-L1, while 63% of HPV-associated tumors and 27% of other histotype tumors did not (odds ratio, 1.35; P = .002 when compared for HPV-associated groups vs all others). Similarly, PD-L1-positive tumors had a 3.61-times higher chance of being node positive than PD-L1-negative tumors (P = .0009). In addition, PD-L1 high-positive tumors had a 5-times higher chance of being p16ink4a negative than PD-L1 low-positive tumors (P = .004). The PD-L1-positive tumors had a lower overall survival and cancer-specific survival than PD-L1-negative tumors. CONCLUSIONS: Overall, PD-L1 expression is associated with high-grade and metastatic tumors. Lower PD-L1 expression is observed more frequently in HPV-associated (warty or basaloid) subtypes than in other, predominantly HPV-independent types. As a result, PD-L1 positivity, including higher expression, portends lower overall and cancer-specific survival. These data provide a rational for further investigating PD-L1-based immunotherapeutics in PC.
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