Prognostic values and clinical implications of programmed cell death-ligand 1 (PD-L1), fork head transcription factor P-1 (FOXP-1) and signal transducer and activator of transcription-3 (STAT-3) expression in diffuse large B-cell lymphoma (DLBCL); an immunohistochemical study

Abstract

Context PD-L1 is an inhibitory ligand that functions as an essential immune checkpoint. FOXP-1 is a member of the FOXP family. STAT-3 plays a critical role in regulation of cell proliferation and survival. The detailed expression of the three markers together in DLBCL tissues and their prognostic value in patients with DLBCL were not fully investigated. Aim was to assess the expression of PD-L1, FOXP-1 and STAT-3 in diffuse large B-cell lymphoma (DLBCL) and to correlate their expression with the pathological findings, prognostic parameters and clinical implications of patients. Methods PD-L1, FOXP-1 and STAT-3 were assessed in DLBCL tissues derived from 50 patients using immunohistochemistry. Patients were followed up for 3 years for response to therapy progression, recurrence and survival. Results High PD-L1 expression was associated with bone marrow involvement (p = 0.004), extra-nodal involvement (p = 0.006) and advanced stage (p = 0.003). High FOXP-1 expression was associated with presence of bone marrow involvement and high risk group (p < 0.001). High STAT-3 expression was associated with older age of the patient (p < 0.001), presence of bone marrow involvement (p = 0.002), extra-nodal involvement (p = 0.009), and high risk group (p = 0.005). High expression of PD-L1, FOXP-1 and STAT-3 was related to poor response to therapy, poor OS rate and RFS rates (p < 0.001). Conclusion High expression of PD-L1, FOXP-1 and STAT-3 was related poor prognosis in DLBCL patients.

Evaluation of Signal Transducer and Activator of Transcription 3 (STAT-3) Protein Expression in Non-Hodgkin Lymphoma Cases in Hospital USM

“…Between B cell NHL, Ohgami et al found the STAT-3 expression was highest among DLBL (36%) compared to other subtypes [16]. Furthermore, in several studies focusing only on DLBCL, 41% to 84% of cases showed STAT-3 expression in which high STAT-3 expression was observed in 25.7% to 46% of the cases [11,[17][18][19]. While Wu et al and Kwon et al identified 32% and 83% of the DLBCL-NGCB subtype expressed STAT-3 protein, respectively, our study also demonstrated that the DLBCL-NGCB subtype was the highest (20%) among DLBCL subtypes [17,19].…”

“…In contrast, a wide range (6% to 72.4%) of Extra nodal Natural Killer/T cell lymphoma nasal type cases harbored the STAT3 gene mutation [7,20,[22][23][24]. In fact, STAT-3 IHC was reliable as a surrogate marker in routine samples [11,17]. There was no previous study pertaining to the expression of STAT-3 protein in T-lymphoblastic leukemia/lymphoma for comparison.…”

“…STAT-3 staining can be seen in both the nuclear and the cytoplasm. In lymphoma cases, only those with nuclear staining were considered as positive (Figure 2) [11]. The scoring method (Table 1) was utilized [11].…”

“…In lymphoma cases, only those with nuclear staining were considered as positive (Figure 2) [11]. The scoring method (Table 1) was utilized [11]. Age, ethnicity, gender, the localization and size of tumors, B symptoms, lactate dehydrogenase (LDH) level, and the disease stage were included as clinicopathologic features in this study.…”

Programmed death-ligand 1 expression in diffuse large B-cell lymphoma is associated with poor prognosis

“…18 In an Egyptian study, a higher PD-L1 expression was present (38%) in DLBCL patients. 19 It should be noted that different studies used different cutoff values for CPS and TPS. 16 In fact, the choice of cutoff value depends on several factors including the type of antibody used, the staining platform, and the IHC staining protocol.…”