Expression of cyclooxygenase-2 and vascular endothelial growth factor-C correlates with lymphangiogenesis and lymphatic invasion in human gastric cancer.
BACKGROUND
Recent observations have suggested that overexpression of cyclooxygenase-2 (COX-2) promotes tumor lymphangiogenesis through an upregulation of vascular endothelial growth factor-C (VEGF-C) expression. It is unclear whether this mechanism also acts in gastric cancer. The aim of this study was to determine the relationship between COX-2 and VEGF-C expression in human gastric cancer, as well as to correlate with lymph node involvement, prognosis, and other clinicopathologic parameters.


METHODS
Sixty-eight primary gastric cancers were immunohistochemically examined for COX-2, VEGF-C, vascular endothelial growth factor receptor-3 (VEGFR-3, also known as Flt-4), and CD34 expressions. Assessment of Flt-4-positive vessel density (FVD) and microvessel density (MVD) was performed. Then we analyzed their relationships and correlations with clinicopathologic findings and patients' survival time.


RESULTS
The positivity rate of COX-2 and VEGF-C in the primary tumor was 67.7 and 54.4 percent, respectively. A significant correlation was found between the expression of VEGF-C and COX-2, and both were also correlated to MVD, FVD, lymphatic invasion, and TNM stage (p<0.05). COX-2 immunoreactivity was also associated with lymph node metastasis and serosa invasion. Increased MVD was significantly associated with lymph node metastasis and TNM stage. Both COX-2 and VEGF-C expression significantly correlated with poorer prognosis.


CONCLUSIONS
Our data suggest that the expression of COX-2 correlates with VEGF-C expression and both of them correlate with the presence of lymphatic invasion and prognosis in gastric cancer. COX-2-mediated VEGF-C overexpression might promote lymphatic invasion via lymphangiogenesis pathway in patients with gastric cancer.
Da
Ming-Xu
MX
Department of General Surgery, Sun-Yat-Sen Memorial Hospital, Sun-Yat-Sen University, Guangzhou, PR China.
Wu
Xiao-Ting
XT
Wang
Jie
J
Guo
Tian-Kang
TK
Zhao
Zi-Gang
ZG
Luo
Ting
T
Zhang
Ming-Ming
MM
Qian
Kun
K
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D013274:Stomach Neoplasms / Q000401:mortality* / Q000473:pathology*; D042582:Vascular Endothelial Growth Factor C / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; D042582:Vascular Endothelial Growth Factor C; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human