The Expressions And Correlations Of NF-κB,MMP-2 And MMP-9 In Hydatidiform Mole

Objective: Gestational trophoblastic diseases (GTDs) are originated from embryo trophoblast,and they are pregnancy associated diseases, including hydatidiform mole, invasive mole, choriocarcinoma and placental site trophoblastic tumor. The last three are termed gestational trophoblastic tumor (GTT). All invasive mole and around 50% of choriocarcinoma are derived from hydatiform mole. Invasive mole and choriocarcinoma are high malignant tumors characterized by blood vessels erodsion and distant metastasis. They are severly threatening womens'reproductive function and health. So far, it is still not clear about the etiology of malignant transformation of hydatidiform mole. Therefore, to study the mechanism of malignant transformation of hydatidiform mole will help us evaluate the prognosis of hydatidiform mole, provide the evidence for proper clinical treatment as well as reduce the incidence of malignant transformation of hydatidiform mole.Nuclear transcription factor-κB (NF-κB) is a gene transcription factor, which can regulate a wide range of cytokines in immune response, inflammatory response, cell growth and apoptosis, and it is also associated with a variety of tumor metastasis. Studies have shown that NF-κB exists in the human trophoblastic cells, suggesting that NF-κB may play an important role in the pathogenesis of GTD. It has been shown that matrix metalloproteinase-2(MMP-2),matrix metallo proteinase-9(MMP-9)are closely related to tumor metastasis. Therefore, we explored the possible roles of NF-κB, MMP-2 and MMP-9 in malignant transformation of hydatidiform mole by examining the expressions of NF-κB, MMP-2 and MMP-9, as well as their correlations. Our current study will provide a theoretical basis for clinical prevention and treatment of malignant transformation of hydatidiform mole.Methods: 41 cases molar tissues (including 29 cases molar tissues without maliganant transformation and 12 cases molar tissues with maliganant transformation through follow-up visiting) were collected from patients with hydatidiform mole who received initial evacuation in the Third Hospital of Hebei Medical University between 2000-2006, and 17 cases normal villi samples (normal control group) were derived from early pregnant women who received artificial abortion. All 41 cases with complete information and pathologic results were diagnosed according to the diagnostic criteria of trophoblatic diseases proposed by Song Hongzhao. The expressions of NF-κB, MMP-2 and MMP-9 were detected by immunohistochemical staining. Five areas on each section were randomly selected, and HMIAS-2000 image processing system was used to carry out Quantitative gray-scale scanning.The average gray value was used for statistic analysis. The lower the gray value, the higher the protein was expressed.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 Pearson product-moment correlation to setα= 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 expressions and locations of NF-κB, MMP-2 and MMP-9 in tissues: The expression of activated NF-κB was mainly located in cytoplasm of trophoblastic cells and endothelial cells of blood vessels, occasionally found in the nucleus; MMP-2 expression was located in cell membrane and cytoplasm of syncytiotrophoblast and extravillous trophoblastic cells; MMP-9 expression was located in cell membrane and cytoplasm of cytotrophoblast cells3 The gray-scale values of NF-κB positive expressions were 137.82±6.66; 115.55±9.61 and 97.15±11.15, respectively in control group, hydatidiform mole without malignant transformation group and hydatidiform mole with malignant transformation group (F=71.22, P<0.01). The expressions of NF-κB were significantly different between each pair of groups (P<0.05). The lower the gray value, the more protein expressed. The expression of NF-κB in hydatidiform mole with malignant transformation group was much higher than those of control group and hydatidiform mole without malignant transformation group, in addition, the NF-κB expression in hydatidiform mole without malignant transformation group was also higher than that of normal control. The nuclear expression of NF-κB in hydatidiform mole with malignant transformation group was much higher than hydatidiform mole without malignant transformation group with 20% (P<0.05), there is significant difference.4 The gray-scale values of MMP-2 positive expressions were 105.64±5.30; 102.40±7.13 and 70.93±8.87, respectively in control group, hydatidiform mole without malignant transformation group and hydatidiform mole with malignant transformation group (F=103.21, P<0.01). The lower the gray value, the more protein expressed. The expression of MMP-2 in hydatidiform mole with malignant transformation group was much higher than those of control and hydatidiform mole without malignant transformation groups (P<0.05), while, there was no significant difference between hydatidiform mole without malignant transformation group and control group (P> 0.05).5 The gray-scale values of MMP-9 positive expressions were 111.27±4.33; 109.38±5.60 and 86.91±8.81, respectively in control group, hydatidiform mole without malignant transformation group and hydatidiform mole with malignant transformation group (F=69.66, P<0.01). The lower the gray value, the higher protein expression. The expression of MMP-9 in hydatidiform mole with malignant transformation group was much higher than those of control group and hydatidiform mole without malignant transformation group (P <0.05), while, there was no significant difference between hydatidiform mole without malignant transformation group and control group (P>0.05).6 The correlation of NF-κB with MMP-2 and MMP-9 in hydatidiform mole tissues: the expression of NF-κB in hydatidiform mole with malignant transformation group was positive correlated to MMP-2 and MMP-9, respectively (r = 0.890, P<0.01; r =0.713, P<0.01).Conclusion:1 The expressions of NF-κB, MMP-2 and MMP-9 in hydatidiform mole with malignant transformation group were significantly higher than those of control and hydatidiform mole without malignant transformation groups.2 The expression of NF-κB was positively correlated with both MMP-2 and MMP-9 in hydatidiform mole with malignant transformation group, and the nuclear expression of NF-κB was increased, suggesting that the expression of MMP-2 and MMP-9 were regulated by NF-κB.3 To evaluate the prognosis of hydatidiform mole: the expression extensity of NF-κB, MMP-2 and MMP-9 was associated with the prognosis of hydatidiform mole. The prognosis was worse in patients with higher expressions of NF-κB, MMP-2 and MMP-9 mole compared with those with lower expressed mole, and the incidence developing to invasive mole or choriocarcinoma was also higher in these patients. In contrast, the patients with lower levels of NF-κB, MMP-2 and MMP-9 had better prognosis and lower incidence of developing to invasive mole or choriocarcinoma.4 NF-κB, MMP-2 and MMP-9 are involved in malignant transformation of hydatidiform mole, and have an impact on trophoblastic invasion, suggesting that they play an important role in predicating the prognosis of hydatidiform mole.