Expression and Clinical Correlation of PD-1/PD-L1 and VE1(BRAFp.V600E) in Pediatric Langerhans Cell Histiocytosis

Sneha Tandon; Sheila Weitzman; Brooklyn Joyce; Bryan Mcguire; Derek Stephens; James Whitlock; Cynthia Hawkins; Bo Yee Ngan; Oussama Abla

doi:10.4084/MJHID.2023.035

Expression and Clinical Correlation of PD-1/PD-L1 and VE1(BRAFp.V600E) in Pediatric Langerhans Cell Histiocytosis

Mediterr J Hematol Infect Dis. 2023 May 1;15(1):e2023035. doi: 10.4084/MJHID.2023.035. eCollection 2023.

Authors

Sneha Tandon¹, Sheila Weitzman², Brooklyn Joyce², Bryan Mcguire³, Derek Stephens³, James Whitlock², Cynthia Hawkins⁴, Bo Yee Ngan⁴, Oussama Abla²

Affiliations

¹ Division of Paediatric Hematology/Oncology, The Royal London Hospital, Barts Health NHS Trust, London, United Kingdom.
² Division of Hematology/Oncology, The Hospital for Sick Children, University of Toronto, Canada.
³ Department of Biostatistics, The Hospital for Sick Children, University of Toronto, Canada.
⁴ Division of Pathology, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, University of Toronto, Canada.

Abstract

Background and objectives: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm with a wide spectrum of clinical presentations. Programmed Cell Death-1 (PD-1) receptor and its ligand (PD-L1) are overexpressed in LCH, but their clinical significance is unknown. We performed a clinical correlation study of PD-1/PD-L1 and VE1(BRAFp.V600E) expression in 131 children with LCH.

Methods: A total of 111 samples were tested for PD-1/PD-L1 and 109 for VE1(BRAFp.V600E) mutant protein by immunohistochemistry.

Results: PD-1, PD-L1 and VE1(BRAFp.V600E) positivity was observed in 40.5%, 31.53% and 55%, respectively. PD-1/ PD-L1 expression showed no significant effect on the rate of disease reactivations, early response to therapy or late sequelae. The 5-year EFS was not statistically different between patients with PD-1 positive compared to those with PD-1 negative tumours (47.7% vs.58.8%, p=0.17). Similar 5-year EFS rates were also seen in those who were PD-L1 positive compared to PD-L1 negative cases (50.5% vs.55.5%, p=0.61). VE1(BRAFp.V600E) positivity was associated with a significantly higher frequency of risk-organ involvement (p=0.0053), but no significant effect on early response to therapy or rates of reactivations or late sequelae.

Conclusions: Our study showed no significant correlation between VE1(BRAFp.V600E) expression, PD-1 and PD-L1 and clinical outcome in pediatric LCH.

Keywords: BRAF-V600E; Histiocytosis; Langerhans cell histiocytosis; PD-1; PD-L1; Pediatric; VE1.