J Pathol Transl Med.  2017 Mar;51(2):152-158. 10.4132/jptm.2016.11.03.

GLUT1 as a Prognostic Factor for Classical Hodgkin's Lymphoma: Correlation with PD-L1 and PD-L2 Expression

• Koh YW
• Han JH
• Park SY
• Yoon DH
• Suh C
• Huh J

• KMID: 2372964
• DOI: http://doi.org/10.4132/jptm.2016.11.03

Abstract

BACKGROUND
Glucose transporter type 1 (GLUT1) expression is linked to glucose metabolism and tissue hypoxia. A recent study reported that GLUT1 was significantly associated with programmed death ligand 1 (PD-L1) as a therapeutic target in relapsed or refractory classical Hodgkin's lymphoma (cHL). The purpose of this study was to measure the expression of GLUT1 and assess its prognostic significance and potential relationships with PD-L1, programmed death ligand 2 (PD-L2), and programmed death-1 (PD-1) expressions in cHL.
METHODS
Diagnostic tissues from 125 patients with cHL treated with doxorubicin, bleomycin, vinblastine, and dacarbazine were evaluated retrospectively via immunohistochemical analysis of GLUT1, PD-L1, PD-L2, and PD-1 expression.
RESULTS
The median follow-up time was 4.83 years (range, 0.08 to 17.33 years). GLUT1, PD-L1, PD-L2, and PD-1 were expressed in 44.8%, 63.2%, 9.6%, and 13.6% of the specimens, respectively. Positive correlations were found between GLUT1 and PD-L1 expression (p = .004) and between GLUT1 and PD-L2 expression (p = .031). GLUT1 expression in Hodgkin/Reed-Sternberg (HRS) cells was not associated with overall survival or event-free survival (EFS) in the entire cohort (p = .299 and p = .143, respectively). A subgroup analysis according to the Ann Arbor stage illustrated that GLUT1 expression in HRS cells was associated with better EFS in advanced-stage disease (p = .029). A multivariate analysis identified GLUT1 as a marginally significant prognostic factor for EFS (p = .068).
CONCLUSIONS
This study suggests that GLUT1 expression is associated with better clinical outcomes in advanced-stage cHL and is significantly associated with PD-L1 and PD-L2 expressions.

Keyword

Hodgkin lymphoma; GLUT1; Programmed death ligand 1; Programmed death ligand 2; Programmed death-1

Figure

• 

  Fig. 1. Glucose transporter type 1 (GLUT1), programmed death ligand 1 (PD-L1), programmed death ligand 2 (PD-L2), and programmed death-1 (PD-1) expression in classical Hodgkin’s lymphoma tissues. (A) High GLUT1 expression in Hodgkin/Reed–Sternberg (HRS) cells (≥ 20%). (B) High PD-L1 expression in HRS cells (≥20%). (C) High PD-L2 expression in HRS cells (≥20%). (D) High PD-1 expression in the peritumoral microenvironment (≥20%).

• 

  Fig. 2. Comparison of survival rates according to glucose transporter type 1 (GLUT1) expression in advanced-stage classical Hodgkin’s lymphoma. The event-free survival rate is significantly higher in the GLUT1-positive group than in the GLUT1-negative group (A). GLUT1 expression is not significantly associated with the overall survival rate (B).

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