Overexpression of GRP78 in complete hydatidiform moles

ObjectiveHydatidiform moles, subdivided into partial moles (PM) and complete moles (CM), are abnormal pregnancies with a disturbed invasive behavior. We had previously shown that MMP-2 and p53 proteins are overexpressed in CM versus PM, and that in primary cytotrophoblasts p53 protein is stabilized by complexing to the 78 kDa glucose-regulated protein (GRP78) which is involved in cytotrophoblasts invasion process. The present study aims to compare the transcript expression profile of p53, MMP-2 and GRP78 in hydatidiform moles.MethodsA retrospective study was performed by RT-qPCR and immunostaining on paraffin-embedded tissues of 19 PM, 16 CM and 16 control (CTRL) samples of gestational age 8–12 weeks.ResultsExpression of MMP-2 transcript was significantly overexpressed in CM compared to CTRL samples (p = 0.031). In contrast, expression of p53 transcript was similar among the samples. This suggests a regulation of p53 in CM at the protein level. GRP78 cDNA was significantly overexpressed in CM compared to CTRL (p = 0.021) and to PM (p = 0.011). At the protein level, immunostaining of GRP78 was on average stronger in CM than PM samples.ConclusionsCollectively, present data suggest that in CM, p53 is normally expressed at the mRNA level but probably complexes at the protein level with the overexpressed GRP78, leading to accumulation of p53 protein. Moreover, since GRP78 and MMP-2 are increased in CM and known to play key roles in invasion, our results suggest that GRP78 and MMP-2 should be investigated as prognostic markers of hydatidiform moles.

► MMP2 and GRP78 (mRNA and protein) overexpressed in complete moles (CM).
► p53 protein, able to bind GRP78 and regulate MMP2 expression, stabilized in CM.
► MMP2 and GRP78, key players in trophoblast invasion, as potent markers of moles.