title: Elevated platelet-derived growth factor-B in congenital cystic adenomatoid malformations requiring fetal resection.
abstract: BACKGROUND
  During lung development, platelet-derived growth factor-BB (PDGF-BB) is maximal during the canalicular stage and decreases by the saccular stage. PDGF-BB stimulates lung growth by increasing cell proliferation. Fetal CCAMs have been shown to have an elevated proliferative index, but it is not known why some CCAMs rapidly enlarge in utero and cause fetal hydrops. The authors hypothesized that the high proliferative index and rapid enlargement of some fetal CCAMs may be caused by persistently elevated PDGF-BB production compared with normal fetal lung.
  
  
  METHODS
  To test this hypothesis, tissue was obtained at the time of resection from two fetal CCAMs (22 weeks), three full-term CCAMs, and three normal fetal lungs (21 to 22 weeks). PDGF-BB production by fetal CCAMs was compared with normal age-matched fetal lung using immunohistochemistry, reverse transcriptionase-polymerase chain reaction (RT-PCR), and Western blot analysis.
  
  
  RESULTS
  CCAMs resulting in fetal hydrops and requiring fetal resection had strong mesenchymal immunostaining for PDGF-BB next to epithelial lined cysts, increased PDGF-B gene expression by RT-PCR, and elevated PDGF-BB protein by Western blot, compared with normal age-matched fetal lung. Term CCAMs had minimal PDGF-BB staining, PDGF-B gene expression, and PDGF-BB protein production.
  
  
  CONCLUSIONS
  CCAMs that grew rapidly and progressed to hydrops, requiring in utero resection, demonstrated increased mesenchymal PDGF-B gene expression and PDGF-BB protein production compared with age-matched normal fetal lung, which may, in part, be responsible for the autonomous growth and proliferation seen in hydropic fetal CCAMs.
authors.affiliation: The Center for Fetal Diagnosis and Treatment, The Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine, 19104, USA.
authors.forename: K W
authors.initials: KW
authors.lastname: Liechty
authors.forename: T M
authors.initials: TM
authors.lastname: Crombleholme
authors.forename: T M
authors.initials: TM
authors.lastname: Quinn
authors.forename: D L
authors.initials: DL
authors.lastname: Cass
authors.forename: A W
authors.initials: AW
authors.lastname: Flake
authors.forename: N S
authors.initials: NS
authors.lastname: Adzick
mesh_terms: D015153:Blotting, Western; D015615:Cystic Adenomatoid Malformation of Lung, Congenital / Q000097:blood* / Q000150:complications / Q000601:surgery; D018450:Disease Progression; D005333:Fetus / Q000601:surgery*; D015870:Gene Expression; D006801:Humans; D015160:Hydrops Fetalis / Q000209:etiology; D007150:Immunohistochemistry; D007231:Infant, Newborn; D008168:Lung / Q000196:embryology* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D010982:Platelet-Derived Growth Factor