The Expressions And Clinical Significance Of P53,Survivin And Cycooxygenase2(COX-2) In Hydatidiform Mole By IHC

Objective: Gestational trophoblastic diseases (GTD), which are derived from embryo trophoblast, include hydatidiform mole, invasive mole, choriocarcinoma and placental site trophoblastic tumor. Trophoblastic cells are specific epithelial cells during implantation and earlier period of placental formation. They proliferate very fast and can invade endometrium like malignant tumor cells, but the invasion of normal trophhoblastic cells is distinctively limited by time and space. Hydatidiform mole is the most common type of gestational trophoblastic disease.The reason of hydatidiform mole was not identified. Compared with trophoblastic cells in normal pregnancy, the trophoblastic cells in hydatidiform mole are characterized by active proliferation. Although hydatidiform mole is benign, it has a potential malignant trend of transformation. At present, there is still no method to prognosticate the malignant transformation of hydatidiform mole in early stage. It is considered that the patients with high risk factors should be administered with chemoprophylaxis, but not necessarily to do so in all hydatidiform mole patients. The tumor suppressor gene P53 is known to play a central role in the protection against the propagation of DNA damage, primarily by inducing cell cycle arrest or apoptosis. Survivin is a member of the inhibitor of apoptosis (IAP) family of proteins. Some researches have found that Survivin played an important role in the gene regulation of cell apoptosis and cell cycle progression. Cyclooxygenase-2 (COX-2) is one of the rate-limiting enzymes, which can catalyze the convertion of arachidonic acid to prostalandins. Many experimental studies have also demonstrated that COX-2 are involved in the tumor invasion, metastasis, cell apoptosis, cell cycle progression and angiogenesis, and that its upregulation is regarded as ratelimiting step of tumor growth. In current study, the expressions and correlation of p53, COX-2 and Survivin were examined in tissues of normal early gestational villi, hydatidiform mole with or without malignant transformation, and the roles of these molecules were explored in pathogenesis as well as malignant proceeding 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 evacuation in the Third Hospital of Hebei Medical University between 2000-2006, and 17 cases normal villi samples (normal control group) derived from early pregnant women who received artifical abortion in 2006. The expressions of p53, Survivin and COX-2 were detected in these tissues by immunohistochemistry. SPSS 12.0 was applied to analyze the experimental results.Results: 1.The positive expression of p53 was localized in nucleus of trophoblasic cells. The positive rates of p53 in normal control group, hydatidiform mole without maliganant transformation group and hydatidiform mole with malignant transformation group were 2/17, 14/29 and 11/12,respectively. There was statistical significance among 3 groups (p<0.01). The difference between normal control group and hydatidiform mole without maliganant transformation group was statistically significant (p<0.05). The difference between normal control group and hydatidiform mole with maliganant transformation group was statistically significant(p<0.01). The difference between hydatidiform mole without maliganant transformation group and hydatidiform mole with maliganant transformation group was significant (p<0.01).2.The positive expression of Survivin was localized in both nucleus and cytoplasm of trophoblasic cells, but mainly in cytoplasm. The positive rates of Survivin in normal control group, hydatidiform mole without maliganant transformation group and hydatidiform mole with malignant transformation group were 4/17, 12/29 and 9/12,respectively. The difference between normal control group and hydatidiform mole without maliganant transformation group was not significant (p>0.05). The difference between hydatidiform mole with malignant transformation group and hydatidiform mole without maliganant transformation group was not significant (p>0.05). The expression of Survivin was significantly higher in hydatidiform mole with malignant transformation group than that in normal control group (p<0.01).3.The positive expression of COX-2 was localized in cytoplasm of trophoblasic cells. The positive rates of COX-2 in normal control group, hydatidiform mole without maliganant transformation group and hydatidiform mole with malignant transformation group were 6/17, 17/29 and 11/12, respectively. There was statistical significance among 3 groups (p<0.05). The difference between normal control group and hydatidiform mole without maliganant transformation group was not significant (p>0.05). The difference between hydatidiform mole with malignant transformation group and hydatidiform mole without maliganant transformation group was not significant (p>0.05). The expression of COX-2 was significantly higher in hydatidiform mole with malignant transformation group than those of normal control group (p<0.01).4.There was no correlation between the expressions of COX-2 and p53 in hydatidiform mole(r=0.362,p>0.05). However, there was a significant correlation between the expressions of Survivin and p53 (r=0.297,p<0.05) in hydatidiform mole.Conclusion: 1.The higher expression of p53 in hydatidiform mole with malignant transformation indicates that it plays an important role in trophoblatic cell proliferation, and over-expression of p53 may involve in the invasive behavior of hydatidiform mole. A suitable-expression of Survivin in normal early gestation villi may be crucial for embryo karyokinesis and cell proliferation, while an over-expression of Survivin in GTDs may play an important role in their oncogenesis. Over -expression of COX-2 may involve in the development and invasive behavior of Gestational trophoblastic diseases.2.The over-pressions of Survivin, p53 may play an important role in the carcinogenesis and progress of malignant transformation of hydatidiform mole through promotion of proliferation and inhibition of apoptosis. They may play synergetic roles in the process of malignant transformation of hydatidiform mole. The detection of Survivin, p53 is helpful to evaluate the biological behavior of trophoblastic cells in patients with hyditiform mole.