title: Expressions of COX-2 and VEGF-C in gastric cancer: correlations with lymphangiogenesis and prognostic implications.
abstract: BACKGROUND
  Cyclooxygenase-2 (COX-2) has recently been considered to promote lymphangiogenesis by up-regulating vascular endothelial growth factor-C (VEGF-C) in breast and lung cancer. However, the impact of COX-2 on lymphangiogenesis of gastric cancer remains unclear. This study aims to test the expression of COX-2 and VEGF-C in human gastric cancer, and to analyze the correlation with lymphatic vessel density (LVD), clinicopathologic features and survival prognosis.
  
  
  METHODS
  Using immunohistochemistry, COX-2, VEGF-C and level of LVD were analyzed in 56 R0-resected primary gastric adenocarcinomas, while paracancerous normal mucosal tissues were also collected as control from 25 concurrent patients. The relationships among COX-2 and VEGF-C expression, LVD, and clinicopathologic parameters were analyzed. The correlations of COX-2, VEGF-C and level of LVD with patient prognosis were also evaluated by univariate tests and multivariate Cox regression.
  
  
  RESULTS
  The expression rates of COX-2 and VEGF-C were 69.64% and 55.36%, respectively, in gastric carcinoma. Peritumoral LVD was significantly higher than that in both normal and intratumoral tissue (P < 0.05). It was significantly correlated with lymph node metastasis and invasion depth (P = 0.003, P = 0.05). VEGF-C was significantly associated with peritumoral LVD (r = 0.308, P = 0.021). However, COX-2 was not correlated with VEGF-C (r = 0.110, P = 0.419) or LVD (r = 0.042, P = 0.758). Univariate analysis showed that survival time was impaired by higher COX-2 expression and higher peritumoral LVD. Multivariate survival analysis showed that age, COX-2 expression and peritumoral LVD were independent prognostic factors.
  
  
  CONCLUSIONS
  Although COX-2 expression was associated with survival time, it was not correlated with VEGF-C and peritumoral LVD. Our data did not show that overexpression of COX-2 promotes tumor lymphangiogenesis through an up-regulation of VEGF-C expression in gastric carcinoma. Age, COX-2 and peritumoral LVD were independent prognostic factors for human gastric carcinoma.
authors.affiliation: Center of Medical Oncology, West China Hospital, Sichuan University, PR China.
authors.forename: Hong-Feng
authors.initials: HF
authors.lastname: Gou
authors.forename: Xin-Chuan
authors.initials: XC
authors.lastname: Chen
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
authors.forename: Ming
authors.initials: M
authors.lastname: Jiang
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.forename: Dan
authors.initials: D
authors.lastname: Cao
authors.forename: Mei
authors.initials: M
authors.lastname: Hou
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; D042582:Vascular Endothelial Growth Factor C; C500987:monoclonal antibody D2-40; D051546:Cyclooxygenase 2