The present study was undertaken to assess the role of tumor associated urokinase-type plasminogen activator (uPA) and tumor infiltrating granulocyte-derived elastase as a positive and a negative predictor for lymph node involvement in patients with stage II cervical cancer of the uterus. uPA and uPA binding proteins (uPA receptors) were quantitated enzymologically and/or immunologically in cell membrane preparations obtained from cancer tissues. The cell membrane preparations express pro-uPA/uPA, uPA is bound to a specific type of surface receptors, of which more than 50% are saturated. Most of the receptor-bound uPA is enzymologically inactive pro-uPA. We have investigated the localization of pro-uPA/uPA and granulocyte elastase immunohistochemically and semiquantitated in formalin-fixed paraffin-embedded tissue sections in 13 patients with pelvic lymph node involvement and in 16 cases without lymph node involvement. Strong uPA staining was found in areas with invasive growth and degradation of surrounding normal tissue. A significant higher lymph node positive rate was observed in patients who had tumors with strong uPA staining than in those with weak staining (p<0.05). In contrast, phagocytic cells were found close to the tumor cells, and were located in aggregates or diffusely spread within tumor stroma surrounding the tumor nests. The inflammatory reaction seems to be most intense at the border between surrounding normal stromal cells and malignant epithelial cells. These cells produced and secreted granulocyte elastase.

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