Open AccessUrokinase‐type plasminogen activator expression correlates with tumor angiogenesis and poor outcome in gastric cancer
Author(s) -
Kaneko Takeshi,
Konno Hiroyuki,
Baba Megumi,
Tanaka Tatsuo,
Nakamura Satoshi
Publication year - 2003
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2003.tb01350.x
Subject(s) - urokinase receptor , angiogenesis , plasminogen activator , vascular endothelial growth factor , cancer , pathology , cancer research , plasminogen activator inhibitor 1 , lymph node , urokinase , stromal cell , tumor progression , lymphovascular invasion , medicine , cancer cell , biology , metastasis , vegf receptors
Urokinase plasminogen activating system (PA system) and vascular endothelial growth factor (VEGF) were recently suggested to contribute synergistically to tumor progression. To evaluate the roles of the PA system and VEGF in gastric cancer, the effects of the PA system and VEGF on tumor angiogenesis and the survival of patients with gastric cancer were investigated. Cancer tissues from 101 gastric cancer patients were assayed immunohistochemically for expression of urokinase‐type plasminogen activator (uPA), uPA receptor (uPAR), PA inhibitor‐1 (PAI‐1) and VEGF protein. The positive rates of uPA, uPAR, PAI‐1, VEGF expression were 22.8%, 32.7%, 36.6% and 26.7%, respectively. Positive staining was observed in tumor cells (uPA, uPAR, VEGF), or in both tumor cells and stromal cells (PAI‐1). The expressions of uPA, uPAR, PAI‐1 and VEGF were significantly correlated with the clinicopathological factors: uPA, depth of tumor invasion, differentiation, lymphatic and vascular invasion; uPAR, tumor size, depth, lymph node involvement, differentiation, vascular invasion; PAI‐1, tumor size, depth, lymph node involvement, differentiation, vascular invasion; VEGF, differentiation, vascular invasion. The microvessel density (MVD) assessed immunohistochemically was significantly higher in the patients with expression of uPA, uPAR or VEGF, and stepwise analysis identified uPA as an independent correlated factor with MVD. Furthermore, multivariate analysis demonstrated that depth of tumor invasion, lymph node involvement and uPA expression were independent prognostic factors. uPA is a key factor in the PA system, being associated with a poor outcome of gastric cancer, and contributing not only to invasive activity, but also to angiogenesis. (Cancer Sci 2003; 94: 43–49)