Apoptosis in gestational trophoblastic disease is correlated with clinicaloutcome and Bcl-2 expression but not Bax expression

Apoptosis has been found to play a crucial role in the pathogenesis and pro gnosis of many human diseases. The pathogenesis of gestational trophoblasti c disease (GTD), which encompasses hydatidiform moles (HMs) and choriocarci nomas (CCAs), is not fully understood. Prognostic indicators of HM have als o been scanty. In this study, we investigated apoptotic activity and the ex pression of two apoptosis regulatory genes, Bcl-2 and Bax in an attempt to determine the role of apoptosis in GTD, Formalin-fixed paraffin-embedded ti ssue of 33 normal placentas, 14 spontaneous abortions, 14 partial moles, 34 complete moles, and eight CCAs were examined. Apoptotic activity was asses sed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine trip hosphate nick end labeling (TUNEL) method. Quantitative assessment of apopt otic index (AI) was calculated as a percentage of TUNEL-positive nuclei. Ex pression of Bcl-2 and Bax were assessed immunohistochemically, Extensive ap optosis was located in syncytiotrophoblasts, cytotrophoblasts, and villous stromal cells in all HM cases. Apoptosis was detected at a much lower level in spontaneous abortions and normal placentas. Moreover, in normal placent as, TUNEL positive nuclei were exclusively found in syncytiotrophoblasts. A Is were significantly different among Various categories of trophoblastic l esions (P <.001) in an ascending order: normal placentas less than spontane ous abortions less than CCAs less than HMs. Further-more, AIs of those case s that spontaneously regressed was statistically higher than those that dev eloped persistent trophoblastic disease requiring chemotherapy. AIs of trop hoblastic lesions in general inversely correlated with Bcl-2 expression (P <.001), but no significant correlation was found between AI and Bax express ion (P >.5). We conclude that Al may be a useful prognostic marker for clin ical progress of HMs. Bcl-2 expression is probably regulating apoptosis in normal placentas and GTD, whereas Bax expression is not. The difference in Al and Bcl-2 expression between non-molar placentas and HMs offers a potent ial adjunctive diagnostic tool to distinguish the two entities.