Article
E-selectin represents an anti-angiogenic target for intestinal gastric cancer
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Published: | October 1, 2007 |
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Introduction: Gastric cancer, one of the leading cancers worldwide, is associated with poor prognosis, which could not be improved using standard chemotherapy. Angiogenesis and the molecular phenotype of the tumor vasculature determine tumor growth and metastasis and might represent new targets in anti-gastric cancer therapy similar as successfully demonstrated in colorectal carcinoma.
Materials and methods: In a series of 58 gastric cancer patients the endothelial phenotype in normal, inflamed and malignanta gastric tissues was compared using immunoperoxidase staining. Vascular phenotyping included the markers CD31, CD62E and CD62P, CD106, CD54 and HLA-DR. Positive vessels were counted in hot spot regions (standardized field size, magnification x200). Vascular quantification was correlated with a panel of clinical and pathological parameters. Statistical analysis included the Mann-Whitney U test, the Spearman rank correlation coefficient and the Fishers exact probability test.
Results: E-selectin (CD62E), but not P-selectin (CD62P), VCAM-1 (CD106), ICAM-1 (CD54) and HLA-DR, was differentially expressed in benign and malignant gastric tissues (p=0.001). De novo expression of E-selectin on tumor associated vessels was found in 36.2% of the gastric carcinomas and was preferentially observed in vascular rich (>25 CD31 positive vessels) primary tumors (p=0.0043). Similar to the findings in the benign gastric mucosae, no association was found with the inflammatory infiltrate (CD45, CD68) and inflammation activated endothelia in the tumors. E-selectin positive vessels were most frequently observed in cardiac carcinomas (p=0.069). Moreover, the endothelial E-selectin positive phenotype was preferentially detected in the intestinal type of gastric cancer (Laurén, p=0.031) and correlated with tumor cell differentiation (grading, p=0.044). However, the detection of E-selectin positive vessels did not correlate with parameters of tumor progression, such as TNM, tumor relapse or survival.
Discussion: De novo expression of endothelial E-selectin represents a tumor dependent vascular marker in gastric cancer, suggesting this cell adhesion molecule a suitable target for more effective anti-gastric cancer strategies.