Ets-1 and VEGF expression correlates with tumor angiogenesis, lymph node metastasis, and patient survival in esophageal squamous cell carcinoma

  • Tina Mukherjee
  • Anupam Kumar
  • Meera Mathur
  • Tushar Kant Chattopadhyay
  • Ranju Ralhan
Original Paper

DOI: 10.1007/s00432-003-0457-3

Cite this article as:
Mukherjee, T., Kumar, A., Mathur, M. et al. J Cancer Res Clin Oncol (2003) 129: 430. doi:10.1007/s00432-003-0457-3

Abstract

Purpose

Esophageal squamous cell carcinoma (ESCC) in the Indian population exhibits insidious symptomatology, late clinical presentation, aggressive behavior, and high propensity for metastasis. Ets-1, a transcription factor, is expressed in esophageal tumors and associated with poor prognosis. The aim of the present study was to determine the relationship between Ets-1 expression, tumor angiogenesis [vascular endothelial growth factor (VEGF) and microvessel density (MVD)] and the biological behavior of ESCCs.

Methods

In a prospective study the expression of Ets-1, VEGF, and PECAM-1 (CD-31) was determined in 55 ESCCs, by immunohistochemical analysis, correlated with clinicopathological parameters and outcome of the patients.

Results

Overexpression of Ets-1 and VEGF proteins was observed in 44/55 (80%) and 38/55 (69%) of ESCCs, respectively. VEGF immunopositivity was associated with lymph node metastasis (P=0.002). Analysis of mRNA isoforms using RT-PCR revealed increased expression of VEGF 121 transcripts in ESCCs and MVD was correlated with de-differentiation status of the tumors (P=0.049). Kaplan-Meier survival analysis showed significant correlation between poor disease-free survival and tumor stage (P=0.02) and with nodal metastasis (P=0.05). Concomitant expression of VEGF, Ets-1 proteins, and high MVD was correlated with poor disease-free survival (P=0.004).

Conclusion

Significant association of Ets-1 and VEGF proteins with tumor angiogenesis (MVD), lymph node invasion, and poor disease-free survival underscores their relevance regarding aggressive tumor behavior and highlights their potential utility as adverse prognostic factors in esophageal carcinomas.

Keywords

Ets-1 VEGF Angiogenesis Esophageal metastasis Squamous cell carcinoma 

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Tina Mukherjee
    • 1
  • Anupam Kumar
    • 1
  • Meera Mathur
    • 2
  • Tushar Kant Chattopadhyay
    • 3
  • Ranju Ralhan
    • 1
  1. 1.Department of BiochemistryAll India Institute of Medical SciencesAnsari Nagar, New DelhiIndia
  2. 2.Department of PathologyAll India Institute of Medical SciencesIndia
  3. 3.Department of Gastrointestinal SurgeryAll India Institute of Medical SciencesIndia