title: Programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and EBV-encoded RNA (EBER) expression in Hodgkin lymphoma.
abstract: Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) are new targets in cancer immunotherapy. PD-1 protein is an immune checkpoint expressed in many tumors. Epstein-Barr virus (EBV) is present in malignant Hodgkin/Reed-Sternberg (HRS) cells in approximately 40-50 % of Hodgkin lymphoma (HL). The aim of this study is to evaluate the clinical and prognostic importance of PD-1 and/or PD-L1 in HL and also to determine the association between EBV-encoded RNA (EBER) and PD-1/PD-L1. Formalin-fixed, paraffin-embedded tissue samples from 87 cases with HL were analyzed in this study. Immunohistochemical staining was performed to detect the PD-1 and PD-L1 expressions. Chromogenic in situ hybridization for EBER was performed using fluorescein-labeled oligonucleotide probes. PD-1 and PD-L1 expressions were found in 20 % of the cases. The EBER positivity was found in 40 cases (45 %). It has been found that co-expression of PD-1 and PD-L1 was associated with shorter survival although PD-1 or PD-L1 expressions were not found to be related with survival. Overall survival (OS) and disease-free survival (DFS) in cases without PD-1 and PD-L1 expressions were 135 and 107 months, respectively. OS and DFS in cases with co-expression for PD-1 and PD-L1 were 24 and 20 months, respectively, and these differences were found to be statistically significant for both OS and DFS (p = 0.002 and p = 0.003, respectively). Cox regression analysis showed that co-expression of PD-1 and PD-L1 was found to be an independent risk factor for prognosis (OR 6.9, 95 % CI 1.9-24.3). Targeting PD-1 and/or PD-L1 is meaningful due to the 20 % expression of each in HL, and we did not find an important association between PD-1 and PD-L1 and EBER expression in HL. Very poor outcome in cases with co-expression of PD-1/PD-L1 suggests new avenues to detect the new prognostic markers and also therapeutic approaches in HL.
authors.affiliation: Department of Oncology, Cukurova University Faculty of Medicine, Adana, Turkey, sepay@cu.edu.tr.
authors.forename: Semra
authors.initials: S
authors.lastname: Paydas
authors.forename: Emine
authors.initials: E
authors.lastname: Bağır
authors.forename: Gulsah
authors.initials: G
authors.lastname: Seydaoglu
authors.forename: Vehbi
authors.initials: V
authors.lastname: Ercolak
authors.forename: Melek
authors.initials: M
authors.lastname: Ergin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D060890:B7-H1 Antigen / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human; D006689:Hodgkin Disease / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis*; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D012367:RNA, Viral / Q000096:biosynthesis*; D016539:Reed-Sternberg Cells / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C099537:Epstein-Barr virus encoded RNA 1; D009363:Neoplasm Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D012334:RNA, Neoplasm; D012367:RNA, Viral