Increased Activity of Insulin-like Growth Factor binding Protein-4 Protease in H-mole Patients / 대한내분비학회지

ABSTRACT

BACKGROUND: Hydatidiform mole (H-mole) is characterized by the neoplastic proliferation of trophoblasts. Only 1~10% of patients with partial H-mole will develop a trophoblastic tumor, but 18~29% of those with complete H-mole will develop a persistent trophoblastic tumor. Therefore, the early diagnosis and monitoring after operation of an H-mole disease are very important. Recently, the pregnancy associated plasma protein-A (PAPP-A) was proved to have a similar role as that of IGF binding protein-4 (IGFBP-4) protease, which has shown an increasing function in fetal growth and development by degradation of IGFBP-4 and an increase in IGF in the serum during pregnancy. Our hypothesis is "the H-mole, which shows placental hyperplasia will also have an IGFBP-4 protease activity, which may be used as in the early diagnosis and monitoring of H-mole disease". METHODS: Serum samples from 6 non-pregnant, 18 pregnant (5 in the 1st trimester, 10 in the 2nd, and 3 in the 3rd), 12 postpartum women and 3 H-mole patients(2 with complete H-mole and 1with partial H-mole) were collected and measured for the -HCG, IGF and PAPP-A levels and IGFBP-4 protease activities by a IGF-II ligand blot analysis and electrophoresis method. The IGFBP-4 protease activity of the serum during normal pregnancy was compared with that of H-mole disease. RESULTS: The results from the in vitro protease assays using recombinant IGFBP-4 determined that IGFBP-4 proteolysis was significantly increased during the first (56%) and second trimesters (90%), but reached a plateau by the third trimester (94%). In H-mole disease diagnosed 11 weeks after conception, the IGFBP-4 proteolytic activity was 97%, which was nearly the same as at terminal pregnancy. This activity gradually decreased to 75% at 1 week, 58.7% at 2 and 33% at 3 weeks after the operation. The -HCG was also decreased from 490,400 to 123,822.7, 1,352.3, and 128.5 mIU/mL at 1, 2 and 3 weeks after the operation, respectively. The PAPP-A level also gradually decreased from 34.87 to 25.5, 12.0 and 2.7 g/mL 1, 2 and 3 weeks after the operation, respectively. However, the IGF decreased from 238.3 to 172.9 ng/mL 1 week after the operation, but increased to 251.4 and 295 ng/mL at 2 and 3 weeks after the operation, respectively. CONCLUSION: These results demonstrated that the IGFBP-4 protease activity was significantly increased during pregnancy, and was extremely elevated durimg the early stages of H-mole disease, but gradually decreased after removal of molar tissue. Therefore, measuring the IGFBP-4 protease activity may play an important role in the early diagnosis and monitoring of H-mole disease