Background: Angiogenesis plays a critical role in the growth and metastasis of tumors. Among several molecules implicated, much evidence indicates that TSP1 is a potent inhibitor of angiogenesis and VEGF is key activator of angiogenesis. We investigated these gene expression levels at each stage of the Barrett's esophagus-dysplasia-adenocarcinoma sequence to study the role of angiogenesis in the process of esophageal carcinogenesis.
Methods: FFPE samples were obtained from 25 patients with non-dysplastic Barrett's esophagus (BE), 20 patients with dysplastic BE, 18 patients with intramucosal carcinoma of esophagus (IMC), and 57 patients with esophageal adenocarcinoma has lymph node metastasis (advanced carcinoma). No samples were taken from the same patient. Gene expression levels of VEGF and TSP1 were determined using laser captured microdissection and quantitative RT-PCR. The Mann-Whitney U test was used to identify significant differences between 2 groups in each gene. Strength of correlation among these gene expressions was tested by Spearman's rank test.
Results: Both VEGF and TSP1 genes expression level were significantly higher in dysplastic BE, IMC, and advanced carcinoma than non-dysplastic BE (VEGF; p=0.011, <0.001, <0.001, TSP1; p<0.001, <0.001, <0.001). VEGF expression level in advanced carcinoma was also significantly higher than dysplastic BE (p=0.025)(Figure). A significant positive correlation was found between VEGF and TSP1 expression in non-dysplastic BE and dysplastic BE stage (non-dysplastic BE; rs=0.788, p<0.001, dysplastic BE; rs=0.795, p<0.001), but there is no correlation in IMC and advanced carcinoma.
Conclusions: VEGF and TSP1 gene expression are associated with Barrett's epithelial malignant transformation. These findings indicate an unbalance between angiogenic activator and inhibitor, which might be a clue to the induction of Barrett's epithelial tumorigenesis.