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Prognostic relevance of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitors PAI-1 and PAI-2 in gastric cancer

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Abstract

Expression of urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator inhibitor-2 (PAI-2) was evaluated in 125 surgically resected gastric cancers by immunohistochemical analysis. Tissue was stained immunohistochemically with a monoclonal antibody against human uPA and monoclonal antibodies against human PAI-1 and PAI-2. In addition, DNA ploidy patterns were determined by cytofluorometer after staining with propidium iodide. We found that 82 (66%) of the 125 gastric cancers expressed uPA as diffuse cytoplasmic staining, as intensely outlined luminal borders. PAI-1 expression was observed in 62 (50%) of 125 gastric cancer as a fine, diffuse and granular pattern in the cytoplasm. PAI-2 expression was observed in 65 (52%) of the 125 gastric cancers as a diffuse cytoplasmic staining. uPA-positive tumours showed a higher incidence of infiltration, lymph node metastasis and peritoneal dissemination than uPA-negative ones. Patients with uPA-positive tumours proved to have a significantly poorer prognosis than those with negative ones. PAI-1-negative tumours showed a higher incidence of liver metastasis and carried a poorer prognosis than PAI-1-positive ones. There was no significant correlation between uPA or PAI-1 expression and DNA ploidy patterns. Conversely, there was no significant relationship between PAI-2 expression and clinicopathological parameters and prognosis. According to the expression of uPA and PAI-1 status, groups of 19 uPA(−)/PAI-1(−), 44 uPA(+)/PAI-1(−), 23 uPA(−)/PAI-1(+) and 39 uPA(+)/PAI-1(+) were subdivided. Tumours with UPA(+)/PAI-1(−) had a significantly higher incidence of liver metastasis, lymph node metastasis and serosal invasion than the other groups of tumours. Patients with uPA(+)/PAI-1(−) tumours had a significantly poorer prognosis than those with uPA(−)/PAI-1(+) tumours. These results indicate that uPA expression is a useful biological prognostic indicator, and that uPA and PAI-1 may play an important part in the tumour progression and metastasis in gastric cancer.

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Authors and Affiliations

  1. The Second Department of Surgery, School of Medicine, Kanazawa University, Takara-machi 13-1, Kanazawa, 920, Ishikawa, Japan

    H. Ito, Y. Yonemura, H. Fujita, K. Tsuchihara, T. Kawamura, N. Nojima & T. Fujimura

  2. Department of Experimental Therapeutics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan

    H. Nose, Y. Endo & T. Sasaki

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  1. H. Ito
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Ito, H., Yonemura, Y., Fujita, H. et al. Prognostic relevance of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitors PAI-1 and PAI-2 in gastric cancer. Vichows Archiv A Pathol Anat 427, 487–496 (1996). https://doi.org/10.1007/BF00199509

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