title: Molecular genotyping of placental site and epithelioid trophoblastic tumours; female predominance.
abstract: To investigate a large series of placental site trophoblastic tumours (PSTT) and epithelioid trophoblastic tumours (ETT) and determine the relationship between their development and the type and sex of both the immediately antecedent and causative pregnancies.
  
  
  
  The antecedent pregnancy was determined from patient records in 92 cases with a confirmed diagnosis of PSTT, ETT or mixed PSTT/ETT. In a subset of 57 cases, type and sex of the causative pregnancy was established by molecular genotyping of tumour tissue microdissected from formalin-fixed, paraffin-embedded blocks.
  
  
  
  The antecedent pregnancy was a normal live birth in 59 (64%) cases, a hydatidiform mole in 19 (21%) and other pregnancy loss in 14 (15%). Where the sex was recorded, 36 (78%) of 46 antecedent normal pregnancies were female, a significantly greater proportion than expected (p<0.0001). Genotyping of 57 cases found 15 (26%) to derive from hydatidiform moles while 42 (74%) arose in non-molar pregnancies. Where the causative pregnancy was non-molar, 38 (91%) tumours arose in female conceptions, significantly greater than expected (p<0.0001). Analysis of short tandem repeats on the X chromosome in three tumours with an XY chromosomal constitution confirmed that the X chromosome was maternal in origin.
  
  
  
  PSTT and ETT predominantly arise in female pregnancies but can develop in male pregnancies. A male derived X chromosome is not required for the development of these tumours. While these tumours are predominantly female it is not because most originate in complete hydatidiform moles.
authors.affiliation: Trophoblastic Tumour Screening & Treatment Centre, Charing Cross Campus, Imperial College London, London W6 8RF, UK. Electronic address: sihao.zhao10@imperial.ac.uk.
authors.forename: Sihao
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Paediatric Laboratory Medicine, UCL Institute of Child Health, London WC1N 3JH, UK. Electronic address: neil.sebire@gosh.nhs.uk.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Sebire
authors.affiliation: Department of Pathology, Imperial College Healthcare NHS Trust, London W12 0NN, UK. Electronic address: Baljeet.Kaur3@imperial.nhs.uk.
authors.forename: Baljeet
authors.initials: B
authors.lastname: Kaur
authors.affiliation: Trophoblastic Tumour Screening & Treatment Centre, Charing Cross Campus, Imperial College London, London W6 8RF, UK. Electronic address: m.seckl@imperial.ac.uk.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Seckl
authors.affiliation: Trophoblastic Tumour Screening & Treatment Centre, Charing Cross Campus, Imperial College London, London W6 8RF, UK. Electronic address: r.fisher@imperial.ac.uk.
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Fisher
mesh_terms: D041321:Chromosomes, Human, X; D041322:Chromosomes, Human, Y; D005260:Female; D005333:Fetus / Q000648:ultrastructure; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D011247:Pregnancy; D012737:Sex Factors; D014328:Trophoblastic Neoplasms / Q000235:genetics* / Q000473:pathology; D018245:Trophoblastic Tumor, Placental Site / Q000235:genetics* / Q000473:pathology
keywords: Epithelioid trophoblastic tumour; Gestational trophoblastic disease; Molecular genotyping; Placental site trophoblastic tumour; Y chromosome