Expression of plasminogen activator inhibitor‐2 in epithelial ovarian cancer: A favorable prognostic factor related to the actions of CSF‐1

• Published in: International journal of cancer 1997-12, Vol.74 (6), p.571-575
• Main Authors: Chambers, Setsuko K., Ivins, Christina M., Carcangiu, Maria L.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Epithelium - metabolism; Epithelium - pathology; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Macrophage Colony-Stimulating Factor - pharmacology; Medical sciences; Middle Aged; Multivariate Analysis; Neoplasm Staging; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Plasminogen Activator Inhibitor 2 - biosynthesis; Prognosis; Tumor Cells, Cultured - drug effects; Tumors
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19971219)74:6<571::AID-IJC2>3.0.CO;2-R

In ovarian cancer cells, the macrophage colony‐stimulating factor‐1 (CSF‐1) induces the release of plasminogen activator inhibitor‐2 (PAI‐2), and high levels of PAI‐2 as well as of CSF‐1 in ovarian cancer ascites are independently correlated with poor outcome. We now study the effect of CSF‐1 on PAI‐2 expression in vitro and the significance of cellular PAI‐2 expression in vivo. Immunohistochemical detection of PAI‐2 was studied in primary and metastatic tissues from 130 epithelial ovarian cancer cases. Kaplan–Meier curves of survival were compared with the results of log‐rank test. The Cox regression model was used for multivariate analysis. The effect of CSF‐1 on PAI‐2 expression in ovarian cancer cells was also examined in vitro. Fifty‐eight percent of the primary tumors and 68% of the metastases expressed PAI‐2. PAI‐2 expression in the metastases of invasive stages III and IV cases was strongly predictive of a prolonged disease‐free and overall survival. This finding was associated with low residual disease and was also an independent factor for disease‐free survival. In vitro, CSF‐1 treatment of ovarian cancer cells resulted in a decrease in cellular staining for PAI‐2 while increasing the release of PAI‐2 into the conditioned medium. In vivo, we also found an inverse correlation between expression of CSF‐1 and that of PAI‐2 in the primary tumors. We thus describe the favorable independent prognosis of cellular PAI‐2 expression in the metastases of ovarian cancer. Moreover, an inverse correlation was observed between CSF‐1 and PAI‐2 expression in vivo. This lends support for a primary role of cell‐surface (vs. secreted)‐mediated events of plasminogen activation in the development of invasive, poor prognostic phenotypes. Int. J. Cancer 74:571–575, 1997.© 1997 Wiley‐Liss, Inc.