Immunohistochemical Expression And Clinical Significance Of Wnt11 And BCL2A1 In Complete Moles

Background:In Asia, the incidence of hydatidiform mole is 7-10 times higher than that of the United States and Europe..In China, the prevalence of hydatidiform mole is about 5.0/1000. Although hydatidiform mole is a kind of benign trophoblastic cell disease (GTD), the majority of hydatidiform mole can regress after aspiration, whereas 10-20% moles developed into post-molar gestational trophoblastic neoplasia (GTN) with persistently raised or rising human chorionic gonadotropin (hCG) level. Like many other tumors, early diagnosis without invasion or metastasis, is of the utmost importance since the prognosis of patients is much better if the tumor is detected at an earlier stage. However, a delay in the diagnosis may increase the patient’s risk of developing GTN, and therefore the prompt identification of GTN is important.Malignant transformation is referred to be a multi-step process and involves multiple genetic changes. Some researchers used microarray analysis to investigate expression profiles of 589 known genes to characterize regulatory circuitry for cell proliferation in complete moles, finding abnormal Wnt signaling pathway. Wnts, a family of secreted glycoprotein, play an important role in axis formation during early embryonic, later organ development and tissue homeostasis by ensuring balanced rates of stem cell proliferation, cell death and differentiation. Ligand such as Wntll can activate non-canonical signaling pathway and then result in some diseases when it expressed abnormally. BCL2A1 is an anti-apoptosis agent of BCL2 protein family which comprises the sentinel network that regulates the mitochondrial or intrinsic apoptotic response. BCL2 is also considered as the apoptotic response to targeted anticancer therapeutics. To date, less is known about Wntll and BCL2A1 in gestational trophoblastic diseases. This study is aimed to investigate both protein expressions in normal first-trimester villi and complete moles, more importantly elucidate their predictive value in malignant transformation of complete mole by exploring the method of immunohistochemistry(IHC).Objective:This study is aimed to investigate Wntll and BCL2A1 immunohisto-chemical expression in complete moles and normal villi, then explore their predictive value for molar malignancy.Methods:The expression of Wntll and BCL2A1 in 84 complete moles and 30 normal first-trimester villi were detected by Envision immunohistochemistry. Immunoreactive quantitation according to the DAB wt% was applied. Data was analyzed using Kruskal-Wallis test, Pearson test and ROC curve.Results:Of 84 complete moles,14 developed to invasive moles,1 transformed to persistent mole and others regressed spontaneously. Both proteins showed cytoplasmic pattern, whereas their protein expression was highest in moles that developed to invasive ones, gradually reduced in spontaneously regressed moles and normal villi (all P<0.01). We considered a 23.17% cut-off value for Wntl 1 DAB wt% and 16.31% for BCL2A1 DAB wt% to assess molar progression to post-molar trophoblastic neoplasia. There was positive correlation between expressions of the two proteins (r=0.403).Conclusion:Our findings demonstrated immunohistochemical expression of Wntll and BCL2A1 in complete moles and normal villi. Both proteins may be included as part of an immunohistochemical panel for villi obtained from initial evacuation to identify post-molar outcome.