Activated Stat3 expression in gestational trophoblastic disease: Correlation with clinicopathological parameters and apoptotic indices

Abstract

Aims: To assess the expression profile of the activated form of signal transducer and activator of transcription (Stat)3 in gestational trophoblastic disease (GTD) and correlate the findings with clinicopathological parameters. Methods and results: By immunohistochemistry, both cytoplasmic and nuclear expression of p-Stat3-Ser 727 was demonstrated in 88 trophoblastic tissues, including placentas and GTD. Nuclear immunoreactivity of p-Stat3-Ser 727 was significantly higher in hydatidiform mole (HM) (P < 0.001) and choriocarcinoma (P = 0.009) when compared with normal placentas. Placental site trophoblastic tumours (PSTT) and epithelioid trophoblastic tumours (ETT) also demonstrated higher nuclear p-Stat3-Ser 727 expression than their normal trophoblast counterparts. Higher p-Stat3-Ser 727 expression was confirmed in choriocarcinoma cell lines, JEG-3 and JAR, than in a normal trophoblast cell line, with both nuclear and cytoplasmic fractions demonstrated by immunoblotting. Spontaneously regressed HM showed significantly increased nuclear and cytoplasmic p-Stat3-Ser 727 immunoreactivity over those that developed gestational trophoblastic neoplasia (GTN) (P = 0.013, P = 0.039). There was a significant positive and inverse correlation between nuclear p-Stat3-Ser 727 immunoreactivity and apoptotic indices [terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labelling and M30 CytoDeath antibody] (P = 0.001, P < 0.001, Spearman's ρ test) and Bcl-2 expression (P = 0.034), respectively. Conclusions: p-Stat3-Ser 727 plays a role in the pathogenesis of GTD, probably through the regulation of apoptosis. p-Stat3-Ser 727 immunoreactivity is a potential marker in predicting GTN in HM. © 2008 The Authors.