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


CONCLUSIONS
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.
Mukherjee
Tina
T
Department of Biochemistry, All India Institute of Medical Sciences, 110029, Ansari Nagar, New Delhi, India.
Kumar
Anupam
A
Mathur
Meera
M
Chattopadhyay
Tushar Kant
TK
Ralhan
Ranju
R
D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D015996:Survival Rate; D014157:Transcription Factors / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A