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Comparative Study
. 2012 May;16(5):956-66.
doi: 10.1007/s11605-011-1814-1. Epub 2012 Jan 19.

Cyclooxygenase isoenzyme-2 and vascular endothelial growth factor are associated with poor prognosis in esophageal adenocarcinoma

M J D Prins  1 , R J J Verhage, F J W ten Kate, R van Hillegersberg
Affiliations
Comparative Study

Cyclooxygenase isoenzyme-2 and vascular endothelial growth factor are associated with poor prognosis in esophageal adenocarcinoma

M J D Prins et al. J Gastrointest Surg. 2012 May.

Abstract

Background: Cyclooxygenase isoenzyme-2 (COX-2) and vascular endothelial growth factor (VEGF) contribute to angiogenesis and are overexpressed in various malignancies. The aim of the study was to evaluate expression, prognostic value and correlation between COX-2 and VEGF expression in esophageal adenocarcinoma (EAC).

Methods: Surgical specimens of 154 patients with EAC were used to construct a tissue micro array (TMA). TMA sections were immunohistochemically stained for COX-2 and VEGF and scored on intensity of staining.

Results: Estimated 5-year cancer specific survival was 37%. High COX-2 and VEGF expression was observed in 39 (26.5%) and in 77 (53.8%) tumors, respectively. Both markers were associated with poor cancer specific survival (p = .022 and p = .004, respectively, log rank). No significant correlation was found between VEGF and COX-2 expression (r = 063; p = .455). In multivariate analysis, high COX-2 expression (HR 1.65; 95% CI 1.04-2.61; p = .034) was associated with overall survival. In patients with T3 tumors, COX-2 expression was an independent prognostic factor for cancer specific survival (HR 1.81 95% CI 1.10-2.95; p = .019).

Conclusions: This is the first study that evaluated the prognostic value and correlation of COX-2 and VEGF expression in a large and homogenous population of patients with EAC. No correlation between COX-2 and VEGF expression was found. Both markers were expressed in EAC and were associated with poor prognosis. The findings support the use of COX-2 and VEGF inhibitors in future clinical studies.

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Figures

Fig. 1
Fig. 1
Representative examples of COX-2 and VEGF staining. a Tumor core showing strong (3+) cytoplasmic and granular COX-2 staining. Stromal tumor cells did not or only slightly stain positive for COX-2. Original magnification (×200). b Magnification (×400) of tumor core shown in a. c Tumor core showing moderate cytoplasmic VEGF staining (2+). Original magnification (×200). d Tumor cells showing weak cytoplasmic VEGF staining (1+). Original magnification (×200)
Fig. 2
Fig. 2
Cancer specific survival according to high and low COX-2 staining. Log rank test was used to compare differences between survival curves
Fig. 3
Fig. 3
Cancer specific survival according to high and low VEGF staining. Log rank test was used to compare differences between survival curves
See this image and copyright information in PMC

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