Thymidine phosphorylase and vascular endothelial growth factor in patients with Stage I lung adenocarcinoma

Cancer. 2002 Feb 15;94(4):1083-93. doi: 10.1002/cncr.10352.

Abstract

Background: Thymidine phosphorylase (TP) has chemotactic activity in endothelial cells in vitro and angiogenic activity in vivo. However, the clinical significance of TP and cooperative roles of TP with other angiogenic factors have remained unclear in nonsmall cell lung carcinoma (NSCLC).

Methods: The authors stained for TP, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) in 132 tumors from patients with Stage I NSCLC. They compared TP, VEGF, and bFGF expression levels with microvessel counts (MVCs), macrophage counts, mast cell counts, and clinical outcomes of patients with Stage I NSCLC.

Results: In adenocarcinoma samples, only stromal cell-TP expression and tumor cell-VEGF expression were associated with MVCs and mast cell counts but not with macrophage counts. In squamous cell carcinoma samples, there were no significant associations of the expression of any examined angiogenic factors with MVCs, mast cell counts, or macrophage counts. More importantly, only among patients with Stage I adenocarcinoma of the lung did patients in the stromal cell-TP positive tumor group and in the tumor cell-VEGF positive tumor group have a significantly worse prognosis compared with patients in the stromal cell-TP negative tumor group and in the tumor cell VEGF negative group, respectively. In addition, among patients with Stage I adenocarcinoma, patients in the stromal cell-TP positive and tumor cell-VEGF positive tumor group had a significantly worse prognosis among the four groups.

Conclusions: TP induction in tumoral stroma, but not in tumor cells, and tumor cell-VEGF induction may promote angiogenesis cooperatively in adenocarcinoma of the lung. Stromal cell-TP expression and tumor cell-VEGF expression may be important prognostic factors in adenocarcinoma of the lung, and stromal cell-TP expression may be a marker of active remodeling stroma in adenocarcinoma of the lung.

MeSH terms

  • Adenocarcinoma / blood supply
  • Adenocarcinoma / physiopathology*
  • Aged
  • Carcinoma, Non-Small-Cell Lung / blood supply
  • Carcinoma, Non-Small-Cell Lung / physiopathology*
  • Endothelial Growth Factors / biosynthesis*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / blood supply
  • Lung Neoplasms / physiopathology*
  • Lymphokines / biosynthesis*
  • Macrophages
  • Male
  • Mast Cells
  • Middle Aged
  • Neovascularization, Pathologic*
  • Prognosis
  • Stromal Cells
  • Survival Analysis
  • Thymidine Phosphorylase / biosynthesis*
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Thymidine Phosphorylase