title: Cyclooxygenase-2 expression correlates with uPAR levels and is responsible for poor prognosis of colorectal cancer.
abstract: Considering recent findings that cyclooxygensase-2 (COX-2) is involved in the progression of colorectal carcinoma (CRC), the role of COX-2 in promoting invasion and angiogenesis was investigated by evaluating the relationship of COX-2 expression to various clinicopathological variables, including plasminogen activating system (PA system) and vascular endothelial growth factor (VEGF). Tumor tissues from 71 patients with CRC were assayed to determine the antigen levels of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor-1 and -2 (PAI-1 and PAI-2), as well as immunohistochemical expression of VEGF. COX-2 was assayed immunohistochemically in 56 patients. COX-2 expression was detected in cancer cells and it was also expressed by stromal cells in some patients. Fourteen patients (25%) were COX-2 positive, whereas 42 were negative. COX-2 expression was significantly related to lymphatic invasion (P = 0.0317), but was not related to microvessel density or VEGF expression. In the PA system, uPAR antigen levels were significantly higher in tumors with COX-2 expression than in tumors without (P = 0.0233). Univariate analysis showed that significant prognostic variables for survival were tumor size, lymph node involvement, lymphatic invasion, vascular invasion, liver metastasis, high uPAR level, and COX-2 expression, but only liver metastasis was an independent prognostic factor (P = 0.0065) in multivariate analysis. COX-2 expression was a more important prognostic indicator than any other factor except liver metastasis (P = 0.0526). The significant relationship between the presence of COX-2 protein and uPAR antigen levels contributed to the enhancement of tumor invasion and the poor outcome in patients with CRC.
authors.affiliation: Second Department of Surgery, Hamamatsu University School of Medicine, Japan. hkonno@hama-med.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Konno
authors.forename: Megumi
authors.initials: M
authors.lastname: Baba
authors.forename: Tuyoshi
authors.initials: T
authors.lastname: Shoji
authors.forename: Manabu
authors.initials: M
authors.lastname: Ohta
authors.forename: Shohati
authors.initials: S
authors.lastname: Suzuki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakamura
mesh_terms: D015179:Colorectal Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D051546:Cyclooxygenase 2; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins; D008833:Microcirculation / Q000473:pathology; D009361:Neoplasm Invasiveness; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D015996:Survival Rate; D013997:Time Factors
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases