Journal List > Korean J Gynecol Oncol Colposc > v.9(2) > 1123951

Kim, Seo, Lee, Moon, Cho, Moon, Kim, Park, and Hwang: Expression of Urokinase-type Plasminogen Activator(uRA), Plasminogen Activator Inhibitor-1(PAI-1) and nm23 protein, as Prognostic Factors in Epithelial Ovarian Cancer


The prognosis of ovarian cancer remains poor, and there is a need to identifiy patients who are less likely to respond to treatment, in the hope that the identification of these patients with a poorer prognosis may allow the administration of more intensive or different treatment. But, most clinical and pathological factors were considered to lack satisfactory predictive power. Recently, essential role of protease in tumor cell invasion and metastasis have been elucidated in tumor biology. Urokinase-type plasminogen activator (uPA) and its inhibitor, plasminogen activator inhibitor-1 (PAI-1), play a key role in tumor-associated proteolysis. Thus, the presence of both uPA and PAI-1 modulates the invasive and metastatic phenotype of cancer cells. Genetically, nm23 protein from chromosome 17q may act independently as a metastasis suppressor. The purpose of this study was to determine the relative predictive power of some of those prognostic variables such as uPA, PAI-1 and nm23 protein in a selected group of patients of ovarian cancer. Immunohistochemical staining was used to determine the overexpression of uPA, PAI-1 and nm23 protein. Specimens were rated positive and negative. Then, scored '1' in case of positive for uPA, PAI-1, and negative for nm23, and '0' in case of negative for uPA, PAI-1, and positive for nm23, respectively. The sum of scores were divided into three groups (I, II and III groups), and compared with clinico-pathologic parameters, clinical response, lymph node metastasis, recurrence and 5-year survival rate, retrospectively. In univariate analysis, the positive rate of uPA was 36% (29/80), that of PAI-1 was 35% (28/80), and the negative rate of nm23 was 43% (34/80). The overexpression of uPA was higher in the low-grade tumor (p=0.0053), the overexpression of PAI-1 was positively correlated with the advanced stage of tumor (p=0.0001), more malignant histologic type (serous) of tumor (p=0.0013) and larger residual tumor mass (>2 cm)(p=0.0480). The overexpression of nm23 protein was negatively correlated with advanced stage of tumor (p=0.0068) and low-grade tumor (p=0.011). In scoring system, the number of patients with first group (I: score 0) was 24, II group (score: 1~2) was 49, and III group (score: 3) was 7. The mean age of patients was 46.4 years and mean follow-up time was 59 months. The rate of lymph node metastasis were 16.7%, 37%, and 75% respectively(p=0.0632). With increasing score in each group, the less clinical response rate was found (75% vs 71% vs 29%, p=0.0532). The 5-year survival rate of each group were 70% in I group, 65% in II group, and 14% in III group(p=0.0096). In conclusion, the scoring system using immunohistochemical staining with rating of overexpression uPA, PAI-1 and nm23 protein may be useful as an important and powerful predictive prognostic indicator in patients with epithelial ovarian cancer.

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