Expression And Significance Of LMP2and PPM1A In Gestational Trophoblastic Disease

Background:Gestational trophoblastic disease (GTD) is defined as consecutive tumor process from placental chorionic villi which includes hydatidiform mole, invasive hydatidiform mole, choriocarcinoma and placental site trophoblastic tumor(PSTT). The latter three are called by a joint name of gestational trophoblastic neoplasia(GTN). Hydatidiform mole, though benign lesions, has the potential risk of malignant transformation. Early diagnosis and treatment have a very important significance to the prognosis of GTN and in improving life quality of patients. It is widely considered that hydatidiform mole with potential malignant transformation can be given preventive chemotherapy, but this method should not be used as a common practice in patients. Thus, we urgently needs to find a marker which can predict the malignant transformation of hydatidiform mole before the rise of serum hCG. We may make use of it to guide clinical work, and achieve early detection and early intervention.It is still unknown about the molecular mechanism of malignant transformation of hydatidifonn mole. The current supposed mechanism is related to abnormality in motility, invasion and migration of trophocytes. Nuclear factor kappa B(NF-kB) is a kind of transcription factors with a number of regulatory functions in immunocytes activation, apoptosis, inflammation, autoimmune diseases and so on. Researches showed that NF-kB was associated with the occurrence, invasion and migration of many tumors and participated in the processes of embryo implantation, malignant transformation of hydatidiform mole and choriocarcinoma. It was indicated that NF-kB may play a role in the pathogenesis of GTD. Low molecular mass polypeptide-2(LMP2) and protein phosphatase1A(PPM1A) are two important regulatory factors in the classical NF-kB pathway. The motility and invasion of trophocytes would be affected greatly by LMP2and PPMIA gene interference or induced by inhibitors. Therefore, both LMP2and PPMIA are likely to be involved in the malignant transformation of hydatidiform mole.Objective:This study is to investigate the expressions of LMP2and PPMIA in normal placental villi and GTD tissues, analyze the correlation of LMP2and PPMIA proteins and correlate their expressions with clinicopathologic parameters, in order to elucidate their predictive value in malignant transformation of hydatidiform mole.Materials and Methods:The expressions of LMP2and PPMIA proteins in196complete hydatidiform moles (in which28cases with malignant transformation),7invasive moles,5choriocarcinomas and20normal chorionic villus were detected with the method of En Vision immunohistochemistry. Their clinicopathologic data were retrospectively analyzed.Results:LMP2and PPMIA proteins expressed in cytotrophoblast, syncytiotropholast and extravillous trophoblast. The level of LMP2expression in deteriorative hydatidiform mole was significantly higher than that in non-deteriorative hydatidiform mole or normal chorionic villi (6.79±2.38,5.26±2.63and3.10±1.65, all P<0.01), while there was no difference compared with GTN (6.42±2.68, P=0.113). The level of PPMIA expression was highest in normal chorionic villi, and decreased gradually in hydatidiform mole (non-deteriorative and deteriorative) and GTN (6.30±2.98,4.93±2.50,4.43±2.04,3.33±2.06, all P<0.01); The level of PPMIA expression in deteriorative hydatidiform mole was significantly lower than that in non-deteriorative hydatidiform mole(P=0.001). The expression of LMP2protein was correlated to theca lutein ovarian cyst. The expression of PPM1A protein was related with uterine size(P<0.05). However, there was no correlation between the expressions of the two proteins (P>0.05)Conclusions:1. That high expression of LMP2and low expression of PPM1A in the first curettage tissues of hydatidiform moles then developed into GTN indicated that both LMP2and PPM1A may involve in the early events of malignant transformation of trophocytes, and they may play an important role in the malignant transformation of hydatidiform mole.2. The expression of LMP2protein was correlated to theca lutein ovarian cyst and the expression of PPM1A protein was related with uterine size, which indicated that both of them may be linked to the prognosis of hydatidiform mole.