title: Correlations between cyclooxygenase-2 expression and angiogenic factors in primary tumors and liver metastases in colorectal cancer.
abstract: BACKGROUND
  Angiogenesis is required for growth and metastasis of colorectal cancer (CRC), and several positive regulators of tumor angiogenesis have been identified. Cyclooxygenase-2 (COX-2), known to be elevated in several human cancers, regulates angiogenesis by inducing angiogenic factors. The aim of this study was to clarify the levels and evaluate the relationships of COX-2, vascular endothelial growth factor A and C, thymidine phosphorylase (TP) and microvascular density (MVD) in paired tissue specimens between primary CRC and corresponding metastatic liver cancer.
  
  
  METHODS
  Tissue samples from pairs of primary tumors and corresponding metastatic liver tumors from 44 patients with CRC were immunohistochemically evaluated for COX-2, VEGF-A, VEGF-C, TP and MVD.
  
  
  RESULTS
  The primary and corresponding metastatic liver tumors tended to show concordant immunoreactivity for COX-2 (P = 0.005, rs = 0.428), VEGF-A (P = 0.039, rs = 0.314), TP (P = 0.005, rs = 0.422) and MVD (P = 0.046, rs = 0.304) by Spearman rank test. The rate of COX-2 immunoreactivity was higher in liver metastases than in primary tumors (P = 0.002), while the rate of VEGF-A was higher in primary tumors than in liver metastases (P = 0.0004). The incidence of TP immunoreactivity and the level of MVD did not differ between primary and metastatic liver tumors (P = 0.247; P = 0.229). Significant correlations were found between COX-2 immunoreactivity and VEGF-A immunoreactivity in metastatic liver tumors (P = 0.033) as well as in primary tumors (P = 0.008).
  
  
  CONCLUSIONS
  The positive correlations between COX-2, VEGF-A, TP and MVD in primary CRC and liver metastasis as demonstrated here will help to predict the angiogenic activity of liver metastasis by analyzing primary tumors, allowing for individualized cancer treatment options.
authors.affiliation: Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Regina Hiromi
authors.initials: RH
authors.lastname: Nakamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uetake
authors.forename: Satoru
authors.initials: S
authors.lastname: Iida
authors.forename: Yanislav Velchev
authors.initials: YV
authors.lastname: Kolev
authors.forename: Labile Togba
authors.initials: LT
authors.lastname: Soumaoro
authors.forename: Yoko
authors.initials: Y
authors.lastname: Takagi
authors.forename: Masamichi
authors.initials: M
authors.lastname: Yasuno
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugihara
mesh_terms: D000328:Adult; D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000032:analysis*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000098:blood supply* / Q000737:chemistry* / Q000201:enzymology / Q000556:secondary; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D013939:Thymidine Phosphorylase / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D042582:Vascular Endothelial Growth Factor C / Q000032:analysis
chemical_list: D043925:Angiogenesis Inducing Agents; D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D051546:Cyclooxygenase 2; D013939:Thymidine Phosphorylase