Macrophage infiltration-associated thymidine phosphorylase expression correlates with increased microvessel density and poor prognosis in astrocytic tumors

Clin Cancer Res. 2001 Dec;7(12):4021-6.

Abstract

Purpose and experimental design: To clarify the significance of thymidine phosphorylase (TP)/platelet-derived endothelial cell growth factor/gliostatin in human glioma, we examined TP expression immunohistochemically in a series of 50 astrocytic tumors and correlated its expression with tumor angiogenesis and apoptosis, as well as prognosis.

Results: The majority of TP-positive cells were of macrophage origin, which was confirmed by immunostaining TP and CD68 on mirror sections. TP expression was significantly associated with glioma malignancy grading, intratumoral microvessel density, and VEGF expression but showed no relationship with apoptotic index or P53 expression. Regardless of glioma grading, patients with TP-positive tumors had a significantly shorter mean survival time than those with TP-negative tumors.

Conclusions: These findings suggest that TP might play a crucial role in angiogenesis during glioma development, and immunodetection of TP is useful for clinical prediction. Further studies are necessary to better elucidate the role of TP in glioma, which may provide insights into adequate TP-targeted therapy.

MeSH terms

  • Antigens, CD / genetics
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Apoptosis
  • Astrocytoma / blood supply
  • Astrocytoma / enzymology*
  • Astrocytoma / mortality
  • Astrocytoma / pathology
  • DNA, Single-Stranded / analysis
  • Endothelial Growth Factors / genetics
  • Humans
  • Lymphokines / genetics
  • Macrophages / pathology*
  • Microcirculation / pathology*
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Thymidine Phosphorylase / analysis
  • Thymidine Phosphorylase / genetics*
  • Time Factors
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • DNA, Single-Stranded
  • Endothelial Growth Factors
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Thymidine Phosphorylase