Ovarian tumors. Prevalence, malignancy risk and significance of the Plasminogen activation system
Abstract: The aims were to assess the prevalence of ovarian tumors in fertile asymptomatic women and to evaluate the risk of ovarian cancer in women with a history of benign ovarian tumors and endometriosis. In order to search for biomarkers in ovarian tumors, the plasminogen activating (PA) system was studied. A random sample of women 25-40 years old was invited to a transvaginal ultrasonography examination. Ovarian cysts were found in 7% (22/335). At follow-up three months later 18 of the 22 cysts had spontaneously disappeared. In a case-control study, The Swedish Hospital Discharge Register, The National Swedish Cancer Register, and the Fertility Register, were used to analyze the risk of developing ovarian cancer in women hospitalized with the diagnoses of ovarian cyst, functional ovarian cyst, or endometriosis. Young women (15 to 29 years old) discharged from hospital for ovarian cysts and functional cysts showed a doubled risk of developing ovarian cancer. Women with ovarian cysts who had undergone ovarian cyst resection or unilateral oophorectomy had a nine times higher risk of developing ovarian cancer. Women with endometriosis had a minor increased risk of ovarian malignancy. The risk of developing ovarian cancer was inversely related to parity and the mean age at diagnosis of ovarian cancer was lower in all three study groups as compared with the control groups. The gene expression of urokinase plasminogen activator (uPA), its receptor (uPAR) and inhibitor (PAI-1) was increased in malignant as compared with benign tumors, and also increased in poorly as compared with well-differentiated malignant tumors. All three mRNA species were mainly found in the stroma in poorly differentiated tumors and metastases. Stromal expression may be induced by the tumor cells. The protein levels of uPA, uPAR, uPA:PAI-1 complex were higher in malignant than in benign ovarian tumors. Furthermore, the protein content of uPA, uPA:PAI-1 complex and also PAI-1 was higher in poorly than in well-differentiated tumors. In contrast, the level of uPAR was lower in poorly than in well-differentiated malignant tumors, and also lower in advanced than in early stages of the disease. This discrepancy may be the result of increased turn-over of uPAR in poorly differentiated tumors. High tumor tissue content of uPAR as well as low content of uPA was associated with longer postoperative survival.
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