Expression of Apoptotic Markers in Molar Pregnancy Correlation with the Prognosis

Abstract

Hydatidiform Mole (HM) is one of the most challenging aspects of pregnancy, known to be associated with the risk of developing choriocarcinoma. About 8-30% of HMs undergo neoplastic transformation. It is characterized by enlarged, edematous and vesicular hydropic chorionic villi, absence of blood vessels and proliferation of trophoblasts to a varying degree. The incidence rate of HM is very high in India (12/1000 pregnancies) as compared to westerns. The HMs that show evidence of proliferative trophoblastic activity even after evacuation, develop persistent trophoblastic disease (PTD), requiring therapeutic interventions. Except for a serial assay of serum and urine hCG levels, there is no reliable alternate marker for prediction. This practice is though reliable, requires tedious, laborious and long- term follow up. Apoptosis is an intrinsic cellular mechanism leading to the self-destruction of cell. It is believed to be physiologically important for normal placental growth and development and its deregulation has been implicated in Gestational Trophoblastic Diseases (GTDs). It has also been hypothesized that some apoptosis regulatory proteins (Bcl-2, Mcl-1, Fas, FasL, Survivin and XIAP) may determine the outcome of HM. These proteins are also known to have significantly higher expression in most of the human malignancies. However, there are scanty reports so far concerning apoptosis in HMs. Hence, the aim of our study was to analyze the expression profiles of proteins involved in apoptosis, emphasizing on their potentials for clinical applications in the early diagnosis or prognosis of molar pregnancy. The expression profiles of Bcl-2, Mc1-1, Fas, FasL, Survivin and XIAP were investigated in 104 HMs and 110 gestational matched controls by Immunohistochemistry, Immunofluorescence and Western blotting analysis. Attempts have also been made to localize these proteins at ultrastructural level using immunogold electron microscopy (IEM). Our results revealed significant decrease in bcl-2 expression which correlated ....