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

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.