The Expressions And Correlations Of IGF-Ⅱ, IGFBP-2 And IGFBP-3 In Hydatidiform Mole

Objective:Gestational trophoblastic diseases (GTDs) is a spectrum of pregnancy related diseases.They are originated from embryo trophoblast, including hydatidiform mole, invasive mole, choriocarcinoma and placental site trophoblastic tumor. The last three are also referred as gestational trophoblastic tumor (GTT). GTT are highly malignant tumors and mostly occurr in childbearing women, and they can metastasize through blood in the early satge. All invasive mole and around 50% of choriocarcinoma are derived from hydatidiform mole.Compared with trophoblastic cells in normal pregnancy, the trophoblastic cells in hydatidiform mole are much more active to proliferate. Although hydatidiform mole is benign, it has a potential malignant trend of transformation. It is considered that the patients with high risk of malignant transformation should be administered with chemoprophylaxis to improve the prognosis. So far it is still not clear about the etiology and mechanism of malignant transformation of hydatidiform mole.Therefore, an exploration of the mechanism of malignant transformation of hydatidiform mole will help us to predict the malignant transformation and guide clinical treatment as well as improve the prognosis of patients.Insulin-like growth factor system (IGFs) plays an important role in regulating cell proliferation, differentiation and tumorigenesis, which greatly influences the growth and development of humans and animals as well as the occurrence and progress diseases. IGF system includes two kinds of peptide growth factors (IGF-I/-II), 2 receptors (IGF- I R and-IIR), 6 closely associated binding proteins (IGFBPs) and the corresponding IGFBP proteases. IGF-I and IGF-II regulate cell mitosis through the IGF-IR. In vitro and in vivo studies have shown that increased expression of IGF-II in invasive trophoblastic cells plays an important role in stimulating trophoblastic cells proliferation and migration as well as vascular remodeling. The combination of IGF-II and IGFBP-2 enhanced invasiveness and migration of trophoblastic cells. IGFBP and IGFBP proteases co-regulated the serum level of IGF-I and-II. Therefore, we explored the possible roles of IGF-II, IGFBP-2, IGFBP-3 in malignant transformation of hydatidiform mole by examining the expressions of IGF-II, IGFBP-2, IGFBP-3 in normal villi and hydatidiform mole tissues. Our current study will provide a theoretical basis for clinical prevention and treatment of malignant transformation of hydatidiform mole.Methods: Molar tissues samples were collected from 50 cases (including 36 cases of molar tissues without maliganant transformation and 14 cases of molar tissues with maliganant transformation through follow-up visiting) were the patients presented with hydatidiform mole and received initial evacuation in the Third Hospital of Hebei Medical University between 2004.1-2008.1, with an average age of 29.5±5.5 years old. Normal villi samples (normal control group) were derived from 32 cases of women in early pregnant women who received artificial abortion with an average age of 26.5±5.5 years old. The expressions of IGF-II, IGFBP-2 and IGFBP-3 were detected by immunohistochemical staining.The experimental results were analyzed by using SPSS 13.0 statistical software. General clinical data were analyzed by using one-way ANOVA, statistical significances were inferred at P<0.05; correlation analysis using Spearman product-moment correlation to set p = 0.05 as a standard of significant differenceResults:1 Comparison of general clinical information: The inter-group age and gestational age were not statistically significant (P> 0.05).2 The expression of IGF-II in each group: IGF-II was mainly localized in cytoplasm of both syncytitrophoblast and cytotrophoblast cell. The positive rates of IGF-II in normal control group, hydatidiform mole without malignant transformation group and hydatidiform mole with malignant transformation were 43.75% (14/32), 69.44% (25/36) and 100%(14/14), respectively. Among the three groups there was a significant difference (χ2 =14.131 P<0.05). The difference between normal control group and hydatidiform mole without malignant transformation group was statistically significant (P<0.05). The difference between normal control group and hydatidiform mole with malignant transformation group was statistically significant(P<0.05). The difference between hydatidiform mole without malignant transformation group and hydatidiform mole with malignant transformation group was statistically significant(P <0.05).3 The expression of IGFBP-2 in each group: IGFBP-2 was localized in cytoplasm of trophoblastic cells and fibrous tissue, but maily in trophoblastic cells. The positive rates of IGFBP-2 in normal control group, hydatidiform mole without malignant transformation group and hydatidiform mole with malignant transformation were 34.375% (11/32), 61.11% (22/36) and 92.86% (13/14), respectively. Among the three groups there was a significant difference (χ2=13.349 P<0.01). The difference between normal control group and hydatidiform mole without malignant transformation group was statistically significant (P<0.05). The difference between normal control group and hydatidiform mole with malignant transformation group was statistically significant(P<0.05). The difference between hydatidiform mole without malignant transformation group and hydatidiform mole with malignant transformation group was statistically significant (P <0.05).4 The expressions of IGFBP-3 in all groups: IGFBP-3 was localized in cytoplasm of trophoblastic cells and occasionally found in fibrous tissue. The positive rates of IGFBP-3 in normal control group, hydatidiform mole without malignant transformation group and hydatidiform mole with malignant transformation were 75% (24/32), 66.67% (24/36) and 28.57% (4/14), respectively. Among the three groups there was a significant difference (χ2=11.204 P<0.01). The difference between normal control group and hydatidiform mole without malignant transformation group was not statistically significant (P>0.05) .The difference between normal control group and hydatidiform mole with malignant transformation group was statistically significant(P<0.05). The difference between hydatidiform mole without malignant transformation group and hydatidiform mole with malignant transformation group was statistically significant(P <0.05).5 The correlation of IGF-II and IGFBP-2 in hydatidiform mole tissues: Spearman rank correlation analysis showed that in hydatidiform mole tissues there were no correlation between the expressions of IGF-II and IGFBP-2 (r = 0.601, P> 0.05).6 The correlation of IGF-II and IGFBP-3 in hydatidiform mole tissues: Spearman rank correlation analysis showed that in hydatidiform mole tissues IGF-II expression showed negative correlation with IGFBP-3 expression (r =- 0.373, P< 0.05).Conclusions:As the important growth factors, IGF-II, IGFBP-2 and IGFBP-3 played an important role in the occurrence of hydatidiform mole and the malignant transformation process. The expressions of IGF-II and IGFBP-2 in hydatidiform mole tissue were significantly stronger than normal chorionic villi in early pregnancy, the higher the degree of malignancy, the more expressions of IGF-II and IGFBP-2. However, in the hydatidiform group, there is no correlation between the expressions of IGF-II and IGFBP-2, suggesting that IGF-II might promote trophoblastic cells invasion and migration independent of IGFBP-2. The expression of IGFBP-3 in the hydatidiform group was decreased with the increased of malignancy. In hydatidiform mole tissues the expressions of IGF-II, IGFBP-3 were negatively correlated, suggesting that IGFBP-3 might inhibit the function of IGF-II in promoting cell proliferation. IGF-II, IGFBP-2 highly expressed in hydatidiform with malignant transformation may serve as the indicators in different stages of gestational trophoblastic disease, and help us assess the prognosis as well as provide evidence for administering clinical therapy.