title: Expression patterns of ERVWE1/Syncytin-1 and other placentally expressed human endogenous retroviruses along the malignant transformation process of hydatidiform moles.
abstract: BACKGROUND
  Up to 20% of hydatidiform moles are followed by malignant transformation in gestational trophoblastic neoplasia and require chemotherapy. Syncytin-1 is involved in human placental morphogenesis and is also expressed in various cancers. We assessed the predictive value of the expression of Syncytin-1 and its interactants in the malignant transformation process of hydatidiform moles.
  
  
  METHODS
  Syncytin-1 glycoprotein was localized by immunohistochemistry in hydatidiform moles, gestational trophoblastic neoplasia and control placentas. The transcription levels of its locus ERVWE1, its interaction partners (hASCT1, hASCT2, TLR4 and DC-SIGN) and two loci (ERVFRDE1 and ERV3) involved the expression of other placental envelopes were assessed by real-time PCR.
  
  
  RESULTS
  Syncytin-1 glycoprotein was expressed in syncytiotrophoblast of hydatidiform moles with an apical enhancement when compared with normal placentas. Moles with further malignant transformation had a higher staining intensity of Syncytin-1 surface unit C-terminus but the transcription level of its locus ERVWE1 was not different from that of moles with further remission and normal placentas. hASCT1 and TLR4, showed lower transcription levels in complete moles when compared to normal placentas. ERVWE1, ERVFRDE1 and ERV3 transcription was down-regulated in hydatidiform moles and gestational trophoblastic neoplasia.
  
  
  CONCLUSIONS
  Variations of Syncytin-1 protein localization and down-regulation of hASCT1 and TLR4 transcription are likely to reflect altered functions of Syncytin-1 in the premalignant context of complete moles. The reduced transcription in gestational trophoblastic diseases of ERVWE1, ERVFRDE1 and ERV3, which expression during normal pregnancy is differentially regulated by promoter region methylation, suggest a joint dysregulation mechanism in malignant context.
authors.affiliation: University of Lyon 1, University Hospital Lyon Sud, Department of Gynecological Surgery and Oncology, Obstetrics, 165, chemin du Grand Revoyet, 69495 Pierre Bénite, France; French Center for Trophoblastic Diseases, University Hospital Lyon Sud, 165, chemin du Grand Revoyet, 69495 Pierre Bénite, France; Joint Unit Hospices Civils de Lyon-bioMérieux, Cancer Biomarkers Research Group, University Hospital Lyon Sud, 165, chemin du Grand Revoyet, 69495 Pierre Bénite, France. Electronic address: pierre-adrien.bolze@chu-lyon.fr.
authors.forename: Pierre-Adrien
authors.initials: PA
authors.lastname: Bolze
authors.affiliation: French Center for Trophoblastic Diseases, University Hospital Lyon Sud, 165, chemin du Grand Revoyet, 69495 Pierre Bénite, France; Department of Pathology, University Hospital of Rouen, F-76031 Rouen Cedex, France. Electronic address: sophie.patrier@chu-rouen.fr.
authors.forename: Sophie
authors.initials: S
authors.lastname: Patrier
authors.affiliation: Joint Unit Hospices Civils de Lyon-bioMérieux, Cancer Biomarkers Research Group, University Hospital Lyon Sud, 165, chemin du Grand Revoyet, 69495 Pierre Bénite, France. Electronic address: valerie.cheynet@biomerieux.com.
authors.forename: Valérie
authors.initials: V
authors.lastname: Cheynet
authors.affiliation: Joint Unit Hospices Civils de Lyon-bioMérieux, Cancer Biomarkers Research Group, University Hospital Lyon Sud, 165, chemin du Grand Revoyet, 69495 Pierre Bénite, France. Electronic address: guy.oriol@biomerieux.com.
authors.forename: Guy
authors.initials: G
authors.lastname: Oriol
authors.affiliation: University of Lyon 1, University Hospital Femme Mere Enfant, Department of Prenatal Diagnosis, 59 Boulevard Pinel, 69500 Bron, France. Electronic address: jerome.massardier@chu-lyon.fr.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Massardier
authors.affiliation: French Center for Trophoblastic Diseases, University Hospital Lyon Sud, 165, chemin du Grand Revoyet, 69495 Pierre Bénite, France. Electronic address: touria.hajri@chu-lyon.fr.
authors.forename: Touria
authors.initials: T
authors.lastname: Hajri
authors.affiliation: Global R&D Immunoassay bioMérieux, Chemin de l'Orme, 69280 Marcy l'Etoile, France. Electronic address: michele.guillotte@biomerieux.com.
authors.forename: Michèle
authors.initials: M
authors.lastname: Guillotte
authors.affiliation: Global R&D Immunoassay bioMérieux, Chemin de l'Orme, 69280 Marcy l'Etoile, France. Electronic address: marc.bossus@biomerieux.com.
authors.forename: Marc
authors.initials: M
authors.lastname: Bossus
authors.affiliation: Department of Genetics, University Hospital of Lyon, 59 Boulevard Pinel, 69500 Bron, France. Electronic address: damien.sanlaville@chu-lyon.fr.
authors.forename: Damien
authors.initials: D
authors.lastname: Sanlaville
authors.affiliation: University of Lyon 1, University Hospital Lyon Sud, Department of Gynecological Surgery and Oncology, Obstetrics, 165, chemin du Grand Revoyet, 69495 Pierre Bénite, France; French Center for Trophoblastic Diseases, University Hospital Lyon Sud, 165, chemin du Grand Revoyet, 69495 Pierre Bénite, France. Electronic address: francois.golfier@chu-lyon.fr.
authors.forename: François
authors.initials: F
authors.lastname: Golfier
authors.affiliation: Joint Unit Hospices Civils de Lyon-bioMérieux, Cancer Biomarkers Research Group, University Hospital Lyon Sud, 165, chemin du Grand Revoyet, 69495 Pierre Bénite, France; EA Pathophysiology of Injury-induced Immunosuppression, University of Lyon1-Hospices Civils de Lyon-bioMérieux, Hôpital Edouard Herriot, 5 Place d'Arsonval, 69437 Lyon Cedex 3, France. Electronic address: francois.mallet@biomerieux.com.
authors.forename: François
authors.initials: F
authors.lastname: Mallet
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011533:Proviruses / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C518353:ERVFRD-1 protein, human; D015686:Gene Products, env; D011257:Pregnancy Proteins; C405335:syncytin
keywords: Choriocarcinoma; Gestational trophoblastic disease; Gestational trophoblastic neoplasia; Human endogenous retroviruses; Hydatidiform mole; Syncytin-1