PD-1 Expression in Pre-Treatment Follicular Lymphoma Predicts the Risk of Subsequent High-Grade Transformation
Received 30 October 2020
Accepted for publication 30 December 2020
Published 18 January 2021 Volume 2021:14 Pages 481—489
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr William Cho
Marie Beck Enemark,1,2,* Ida Monrad,1,* Charlotte Madsen,1 Kristina Lystlund Lauridsen,3 Bent Honoré,4 Trine Lindhardt Plesner,5 Stephen Jacques Hamilton-Dutoit,3 Francesco d’Amore,1 Maja Ludvigsen1,2
1Department of Hematology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 3Department of Pathology, Aarhus University Hospital, Aarhus, Denmark; 4Department of Biomedicine, Aarhus University, Aarhus, Denmark; 5Department of Pathology, Copenhagen University Hospital, Copenhagen, Denmark
*These authors contributed equally to this work
Correspondence: Maja Ludvigsen
Department of Hematology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, C115, Aarhus N 8200, Denmark
Tel +45 22859523
Purpose: Follicular lymphoma (FL) is an indolent, yet generally incurable neoplasia with a median survival exceeding 10 years. However, a subset of FL patients experiences histological transformation (HT) to a more aggressive lymphoma, in the majority of cases to diffuse large B-cell lymphoma (DLBCL). This affects both the clinical course and the prognostic outcome, resulting in a markedly reduced survival after transformation. Thus, early risk stratification and prediction of patients at risk of HT would be highly valuable in the clinical setting. Here, we investigated the potential of the immune inhibitory programmed death 1 (PD-1) receptor as a biomarker predictive of HT.
Patients and Methods: Immunohistochemical staining and quantification by digital image analysis of PD-1 was performed on diagnostic tumor-tissue samples from FL patients with and without subsequent transformation (n=34 and n=46, respectively), and on paired samples from the transformed lymphoma (n=34).
Results: At the time of initial FL diagnosis, samples from patients with subsequent HT had significantly higher tumor-tissue expression of PD-1 compared with diagnostic FL samples from patients without subsequent HT (p=0.010). At the time of transformation, PD-1 expression was significantly reduced (p< 0.001). No difference was observed in intra-follicular PD-1 expression at FL diagnosis between samples from patients with or without HT; however, high intra-follicular levels of PD-1 were associated with significantly shorter transformation-free survival times (p< 0.043).
Conclusion: Our data suggest that pre-treatment tumor-tissue PD-1 expression already predicts the risk of subsequent transformation to DLBCL, as early as the time of FL diagnosis.
Keywords: programmed death 1; PD-1, follicular lymphoma; FL, histological transformation; HT
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