J Korean Med Sci.  2011 Apr;26(4):513-520. 10.3346/jkms.2011.26.4.513.

VEGF as a Predictor for Response to Definitive Chemoradiotherapy and COX-2 as a Prognosticator for Survival in Esophageal Squamous Cell Carcinoma

• Yoon MS
• Nam TK
• Lee JS
• Cho SH
• Song JY
• Ahn SJ
• Chung IJ
• Jeong JU
• Chung WK
• Nah BS

• KMID: 1777881
• DOI: http://doi.org/10.3346/jkms.2011.26.4.513

Abstract

We investigated the patterns of pretreatment expression of the epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) by immunohistochemical staining and determined their correlation with treatment response and survival in 44 patients with esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT). The definitive CCRT consisted of a median dose of 54 Gy (range: 40.0-68.4 Gy) and two cycles of concurrent administration of mostly 5-fluorouracil + cisplatinum. High expression of EGFR, VEGF, and COX-2 was found in 79.5%, 31.8%, and 38.6%, respectively. The Cox regression analysis for overall survival (OS) showed that both the treatment response and COX-2 expression were significant. The 3-yr OS rates of patients that achieved a complete response and those that did not were 46.7% and 5.3%, respectively (P = 0.006). The logistic regression analysis for treatment response with various parameters showed that only a high expression of VEGF was significantly associated with a complete response. Unlike other well-known studies, higher expression of VEGF was significantly correlated with a complete response to CCRT in this study. However, higher expression of COX-2 was significantly associated with shorter survival. These results suggest that VEGF might be a predictive factor for treatment response and COX-2 a prognostic factor for OS in patients with ESCC after definitive CCRT.

Keyword

Esophageal Neoplasms; Chemoradiotherapy; Epidermal Growth Factor Receptor; Vascular Endothelial Growth Factor; Cyclooxygenase 2

MeSH Terms

Aged
Antineoplastic Agents/therapeutic use
Carcinoma, Squamous Cell/drug therapy/*mortality/radiotherapy/*therapy
Cisplatin/therapeutic use
Combined Modality Therapy
Cyclooxygenase 2/*metabolism
Drug Therapy, Combination
Esophageal Neoplasms/drug therapy/*mortality/radiotherapy/*therapy
Female
Fluorouracil/therapeutic use
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Neoplasm Staging
Predictive Value of Tests
Radiation Dosage
Receptor, Epidermal Growth Factor/metabolism
Regression Analysis
Survival Rate
Vascular Endothelial Growth Factor A/*metabolism

Figure

• 

  Fig. 1 Overall survival according to the treatment response and the patterns of protein expression: (A) The Kaplan-Meier survival curve shows a significant difference between the patients with a complete response (CR) and those without a complete response. (B, C) the survival analyses of EGFR (B) and VEGF (C) did not show significant differences. (D) The patients with a higher expression of COX-2 show a significantly lower overall survival.

• 

  Fig. 2 Immunohistochemical staining of high and low expression of COX-2 (A, D), EGFR (B, E), and VEGF (C, F).

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