Expression Of Maspin In Gestational Trophoblastic Disease

Objective: Gestational trophoblastic disease(GTD) is a group of pregnancy-related diseases, including hydatidiform mole, invasive mole, choriocarcinoma and placental site trophoblastic tumor. It is believed that the pathogenesis of GTD results from a disruption of the delicate balance and regulation of cellular processes including proliferation, differentiation, apoptosis, and invasion in the trophoblastic cells. Maspin (Mammary Serine Protease Inhibitor) was first reported in 1994 as a serpin with tumor suppressive properties. Maspin was initially isolated through subtractive hybridization and differential display analysis as a 42-kDa protein that is expressed in normal mammary epithelial cells but reduced or absent in breast carcinomas. Further research led to maspin's characterization as a class II tumor suppressor based on its ability to inhibit cell invasion, promote apoptosis, and inhibit angiogenesis. But it's role and mechanism in the tumorigenesis and development of gestational trophoblastic diseases are still unclear. Maspin is a newly discovered tumor suppressor gene whose tumor suppressing mechanism seems to be as complex as the progression of the malignancy itself. Recent studies indicate that the maspin gene is a target for transcriptional activation by p53 and DNA methyltransferase inhibitors. To decipher the mechanism of maspin's inhibitory effece, one needs to concider two important factors. First, the direct effect of maspin is complicated by its multicellular expression pattern. Secondly, since maspin most likely function through its interacting proteins. The expression of Maspin is significantly correlated to the malignant biological behaniors of ovarian and it take part in the tumorigenesis, development and metastasis of endometrial carcinoma. However, the molecular mechanism of gestational trophoblastic disease remains unclear. Using immunohistoche- mical staining, we studied the expression of maspin in hydatidiform moles and gestational trophoblastic neoplasia (GTN) , with normal first trimester placenta used as control. The present study aimed at exploring the molecular mechanisms of tumor metastasis. with a view to gestational trophoblastic disease early diagnosis, early treatment and providing the basis for its gene therapy.Methods: Archival molar tissues which were 10% formalin-fixed paraffin-embedded were collected from the Third Affiliated Hospital of Hebei Medical University, Obstetrics and Gynecology in January 2005 ~ May 2008. They included 30 hydatidiform moles and 10 gestational trophoblastic neoplasia. Among them, 11 cases of the hydatidiform moles group subsequently developed GTN and 19 cases of the hydatidiform moles group did not, in the light of Professor Song Hongzhao trophoblastic disease referred to the diagnostic criteria. The above specimens are verified by experienced pathologists with complete clinicopathologic information, no preoperative radiotherapy and chemotherapy.20 cases of normal first trimester placentas were obtained from the same period in our hospital out-patient, which were terminated due to induced abortion for early pregnancy, used as control. Serial 4 mm sections were made from the 10% formalin-fixed paraffin- embedded tissue. Using immunohistochemical staining, we firstly studied the expression of maspin in 10 cases of GTN ,30 cases of hydatidiform mole and 20 cases of normal first trimester placenta. Comparison of immunostaining percentage between molar and control groups was analyzed by the SPSS 13.0 statistical software analysis system. Differences between groups were analyzed by chi-square test or Fisher exact probability. A P value of less than 0.05 ( P < 0.05) was conside- red as statistically significant.Results :1. In gestational trophoblastic disease as well as in normal first trimester placental tissue, expression of maspin was localized to the cytoplasm or nuclei of the trophoblastic cells. 2. In normal first trimester placenta, hydatidiform mole and gestational trophoblastic neoplasia(GTN) the positive rate of Maspin staining was 95.0%,60.0% and 10.0% respectively. Lower expression of maspin(P<0.05) was found in both hydatidiform mole and GTN as compared to normal first trimester placenta. 3. In complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM) the positive rate of Maspin staining was 56.3% and 62.3% respectively. There is no significant different between CHM and PHM. 4. The positive rate of Maspin protein was 36.4% in with subsequent development of GTN. In those cases without GTN development, the positive rate of Maspin staining was 78.9%. Significantly lower expression of maspin ( P < 0.01) was demonstrated in those cases with subsequent development of GTN compared with those without.Conclusion:1 Lower expression of maspin was found in hydatidiform mole as compared to normal first trimester placenta. Loss of Maspin expression may be associated with invasion and metastasis of trophoblastic disease. 2 Lower expression of maspin was found in gestational trophoblastic neoplasia as compared to normal first trimester placentae. This result suggest that Maspin might be implicated in the processes of tumor cell invasion and metastasis which promoted invasive potential of GTN. 3 Significantly lower expression of maspin was demonstrated in those cases with subsequent development of GTN compared with those without GTN development. The lost of Maspin can lead to the cell malignant change and proliferation, which suggest the poor prognosis of the trophoblastic tumor. The down-regulation of the Maspin expression is involved in the malignant progression of GTD. It may be valuable to detect it for the prediction of malignant transformation and evaluation of prognosis in GTD.