CD163 expression was associated with angiogenesis and shortened survival in patients with uniformly treated classical Hodgkin lymphoma

PLoS One. 2014 Jan 29;9(1):e87066. doi: 10.1371/journal.pone.0087066. eCollection 2014.

Abstract

Background: Recent 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.

Methods: Diagnostic 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).

Results: High 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.

Conclusions: Our 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, CD / genetics*
  • Antigens, CD / immunology
  • Antigens, Differentiation, Myelomonocytic / genetics*
  • Antigens, Differentiation, Myelomonocytic / immunology
  • Antineoplastic Agents / therapeutic use
  • Female
  • Gene Expression
  • Hodgkin Disease / drug therapy
  • Hodgkin Disease / genetics*
  • Hodgkin Disease / immunology
  • Hodgkin Disease / mortality*
  • Humans
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neovascularization, Pathologic*
  • Prognosis
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / immunology
  • Survival Analysis
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor A / immunology

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Antineoplastic Agents
  • CD163 antigen
  • Receptors, Cell Surface
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A

Grants and funding

This study was supported by a grant (2011-090) from the Asan Institute for Life Sciences, Seoul, Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.