CD163 Expression Was Associated with Angiogenesis and Shortened Survival in Patients with Uniformly Treated Classical Hodgkin Lymphoma

Young Wha Koh,Chan-Sik Park,Dok Hyun Yoon,Cheolwon Suh,Jooryung Huh,Erica Villa

doi:10.1371/journal.pone.0087066

Young Wha Koh, Chan-Sik Park + Show 4 more

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https://doi.org/10.1371/journal.pone.0087066

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Abstract

BackgroundRecent studies have reported the prognostic value of tissue-associated magrophages (TAMs) in classical Hodgkin lymphoma (cHL). In addition, TAMs are implicated in the tumor angiogenesis. In this study, we examined the prognostic relevance of TAMs in relation to vascular endothelial growth factor (VEGF) expression and angiogenesis in uniformly treated cases of cHL.MethodsDiagnostic tissue from 116 patients with ABVD-treated cHL was evaluated retrospectively by immunohistochemical analysis for CD68, CD163 and VEGF expression and for CD31 expression as a measure of microvessel density (MVD).ResultsHigh CD163 expression (≥35% of cellularity) correlated with VEGF expression (Pearson’s Chi-square test, P = 0.008) and MVD (Spearman correlation coefficient 0.310, P<0.001). High CD163 expression was associated with inferior event-free survival (EFS, P = 0.005) and overall survival (OS, P<0.001) in univariate analysis. In multivariate analysis, high CD163 expression was strongly associated with inferior EFS (P = 0.043) and OS (P = 0.008). Patients with high MVD had a lower OS than those with low MVD, but the difference was not significant (P = 0.071, respectively). While high expression of CD68 was also associated with inferior EFS (P = 0.007), it showed no correlation with VEGF or MVD.ConclusionsOur data confirms that CD163 expression provides independent prognostic information in cHL. The correlation of CD163 with VEGF expression and MVD suggests the role of CD163-positive cells in tumor angiogenesis of cHL.

Highlights

Classical Hodgkin lymphoma is characterized by the disruption of the normal lymph node architecture by the presence of few of Hodgkin/Reed-Sternberg (HRS) cells in a background of reactive bystander cells mainly composed of T and B lymphocytes, macrophages and other cell types [1]. classical Hodgkin lymphoma (cHL) is associated with high cure rates; despite significant advances in treatment, there remains a significant minority of patients with refractory disease in whom prolonged exposure to initial therapy induces chemo-resistance and unnecessary toxicity [2]
By blocking vascular endothelial growth factor (VEGF) binding to the VEGF receptor, bevacizumab interferes with tumor angiogenesis
We have shown a correlation between microvessel density (MVD) and CD163

Summary

Introduction

Classical Hodgkin lymphoma (cHL) is characterized by the disruption of the normal lymph node architecture by the presence of few of Hodgkin/Reed-Sternberg (HRS) cells in a background of reactive bystander cells mainly composed of T and B lymphocytes, macrophages and other cell types [1]. cHL is associated with high cure rates; despite significant advances in treatment, there remains a significant minority of patients with refractory disease in whom prolonged exposure to initial therapy induces chemo-resistance and unnecessary toxicity [2]. Tumor-associated macrophages (TAMs) in lesional tissues have been shown to be a strong prognostic indicator of cHL by gene expression profile analysis and subsequent immunohistochemical detection using CD68 and CD163 as markers [3,4,5,6]. Vascular endothelial growth factor (VEGF) plays an important role in physiologic and pathologic angiogenesis, including neoangiogenesis in tumors [9,10]. VEGF expression has demonstrated prognostic value in several solid malignancies [11,12]. Recent studies have reported the prognostic value of tissue-associated magrophages (TAMs) in classical Hodgkin lymphoma (cHL). We examined the prognostic relevance of TAMs in relation to vascular endothelial growth factor (VEGF) expression and angiogenesis in uniformly treated cases of cHL

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