The expression of COX-2 and VEGF-C in gastric cancer: correlation with lymphangiogenesis, angiogenesis and clinicopathological parameters

Mirsad Dorić, Dželaludin Junuzović, Edina Lazović-Salčin, Suada Kuskunovic-Vlahovljak, Svjetlana Radović, Nina Čamdžić, Mirsad Babić, Haris Čampara


Introduction: The aims of this study were to investigate the
immunohistochemical expression of cyclooxygenase-2 (COX-
2) and vascular endothelial growth factor-C (VEGF-C), their
correlation with lymphangiogenesis, angiogenesis and clinicopathological
significance in human gastric cancer.
Material and methods: Tissue samples of gastric cancer of 60
patients, who underwent Billroth II resection, were analyzed.
The expression of COX-2 and VEGF-C proteins was calculated
using a semi-quantitative immunoreactive score method.
Quantitative analysis of lymphangiogenesis and angiogenesis
was performed according to the method described by Weidner.
Lymphangiogenesis was evaluated by immunostaining with
D2-40. Angiogenesis was assessed by CD105 immunostaining.
Results: There was a statistically significant difference in the
mean values of COX-2 (p< 0.01) and VEGF-C (p< 0.05) between
gastric cancer samples and in control samples. Angiogenesis
was significantly higher in neoplastic tissue then in control group
(p<0.001). Expression of COX-2 showed a significant positive
linear correlation with angiogenesis (p<0.05). However, COX-2
did not correlate with VEGF-C or lymphangiogenesis. There was
an association between VEGF-C and lymphangiogenesis, but
without statistical significance. Lymphangiogenesis significantly
correlated with lymph node metastasis (p=0.007). Expression of
COX-2 showed significant correlation with type of Bormann’s
classification (p=0.019) and depth of invasion (p=0.03).
Conclusions: The tumor cells are the major source of COX-2
and VEGF-C in gastric carcinomas. Their correlation did not
show that COX-2 overexpression promotes tumor lymphangiogenesis
through augmentation of VEGF-C. The results of this
study suggest that neoangiogenesis is a dominant process during
tumor progression, whereas lymphangiogenesis plays an important
role in lymph node metastasis.
Keywords: angiogenesis, CD105, COX-2, D2-40, gastric cancer,
lymphangiogenesis, VEGF-C

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