Cyclooxygenase-2 expression correlates with uPAR levels and is responsible for poor prognosis of colorectal cancer |
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Authors: | Konno Hiroyuki Baba Megumi Shoji Tuyoshi Ohta Manabu Suzuki Shohati Nakamura Satoshi |
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Institution: | (1) Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan |
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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.
This revised version was published online in July 2006 with corrections to the Cover Date. |
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Keywords: | angiogenesis colorectal cancer cyclooxygenase-2 invasion plasminogen activating system uPAR |
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