title: Overexpression of GRP78 in complete hydatidiform moles.
abstract: OBJECTIVE
  Hydatidiform 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 78kDa 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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  Expression 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.
  
  
  CONCLUSIONS
  Collectively, 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.
authors.affiliation: Department of Obstetrics and Gynecology, Maternity, Geneva University Hospital, 1211 Geneva, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Ribaux
authors.forename: P
authors.initials: P
authors.lastname: Petignat
authors.forename: V
authors.initials: V
authors.lastname: Finci
authors.forename: F Pelluard
authors.initials: FP
authors.lastname: Nehmé
authors.forename: D
authors.initials: D
authors.lastname: Carles
authors.forename: O
authors.initials: O
authors.lastname: Irion
authors.forename: M
authors.initials: M
authors.lastname: Epiney
authors.forename: M
authors.initials: M
authors.lastname: Cohen
mesh_terms: D016022:Case-Control Studies; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D016612:Paraffin Embedding; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D020778:Matrix Metalloproteinase 2