Biopsy specimen microvessel density is a useful prognostic marker in patients with T(2-4)M(0) esophageal cancer treated with chemoradiotherapy

Clin Cancer Res. 2002 Jan;8(1):124-30.

Abstract

Purpose: The purpose of this study was to identify prognostic markers for chemoradiotherapy (CRT) in T(2-4)M(0) esophageal cancer.

Experimental design: We investigated clinicopathological and biological markers in biopsy specimens from 73 T(2-4)M(0) esophageal cancer patients treated with CRT (5-fluorouracil plus cisplatin and 60 Gy of radiation). Expressions of p53 gene product, Ki-67 labeling index, epidermal growth factor receptor, cyclin D1, vascular endothelial growth factor, microvessel density (MVD), thymidylate synthase, dihydropyrimidine dehydrogenase, and glutathione S-transferase pi in formalin-fixed biopsy samples of primary tumors before CRT were examined immunohistochemically. Clinicopathological and biological marker expressions were compared in terms of survival.

Results: Univariate analysis revealed that performance status and T stage in clinicopathological features had a significant association with survival (P = 0.007 and 0.04, respectively) and that patients whose tumors showed high MVD [>median (19.7 vessels)] in biological markers had significantly better survival than those with low MVD (< or = median, P = 0.02). Also, there were weak associations of p53 and Ki-67 with survival (P = 0.08 and 0.07, respectively). Multivariate analysis, using both clinicopathological and biological markers, showed that MVD, T stage, and performance status became independent variables (P = 0.002, 0.02, and 0.02, respectively). Kaplan-Meier analysis showed that the patients with high MVD tumors survived longer than those with low MVD tumors (median survival time, not reached and 13 months, respectively; 3-year survival rate, 61% and 33%, respectively), with a significant difference of P = 0.02.

Conclusions: These results indicate that MVD using pretreatment biopsy specimens is a potentially useful prognostic marker for CRT in patients with T(2-4)M(0) esophageal cancer who are treated with CRT.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Cyclin D1 / metabolism
  • Dihydrouracil Dehydrogenase (NADP)
  • Endothelial Growth Factors / metabolism
  • ErbB Receptors / metabolism
  • Esophageal Neoplasms / blood supply*
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / therapy
  • Female
  • Fluorouracil / administration & dosage
  • Glutathione S-Transferase pi
  • Glutathione Transferase / metabolism
  • Humans
  • Immunoenzyme Techniques
  • Isoenzymes / metabolism
  • Ki-67 Antigen / metabolism
  • Lymphokines / metabolism
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neovascularization, Pathologic / mortality
  • Neovascularization, Pathologic / pathology*
  • Neovascularization, Pathologic / therapy
  • Oxidoreductases / metabolism
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Radiation Dosage
  • Survival Rate
  • Thymidylate Synthase / metabolism
  • Tumor Suppressor Protein p53 / biosynthesis
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Biomarkers, Tumor
  • Endothelial Growth Factors
  • Isoenzymes
  • Ki-67 Antigen
  • Lymphokines
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Tumor Suppressor Protein p53
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Cyclin D1
  • Oxidoreductases
  • Dihydrouracil Dehydrogenase (NADP)
  • Thymidylate Synthase
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Glutathione Transferase
  • ErbB Receptors
  • Cisplatin
  • Fluorouracil