title: Anti-Glypican 3, a Novel Ancillary Maker in the Histological Assessment of Hirschsprung's Disease.
abstract: Hirschsprung's disease (HSCR) results from a malformation of the enteric nervous system. A congenital absence of intrinsic ganglion cells from the distal rectum and a variable length of the contiguous bowel is the required diagnostic feature of Hirschsprung's disease and total colonic aganglionosis (TCA). We evaluated the utility of a monoclonal antibody directed against glypican 3 (GPC-3), a membrane bound protein involved in regulation of the signaling of Wingless-types (WNTs), Hedgehogs (Hh), Fibroblast Growth Factors (FGFs), and Bone Morphogenetic Proteins (BMPs), in the detection of ganglion cells in formalin-fixed, paraffin-embedded tissue sections.
  
  
  
  The presence/absence of ganglion cells was evaluated retrospectively by immunohistochemical staining for calretinin and GPC-3 in tissue specimens; a total of 15 patients who underwent colectomy (total or sub-total) for histologically proven aganglionosis (14 HSCR, 1 TCA) and 5 rectal suction biopsies (4HSCR-B, 1 TCA-B) were considered. Of the 20 considered cases, a total of 60 tissue specimens (3 for each patient) were selected. A total of 30 additional normal (N) colonic mucosa biopsy samples were also included.
  
  
  
  GPC-3 constantly identified ganglion cell bodies in all but 2 normal biopsies (with normal presentation of ganglion cells on hematoxylin and eosin (H&E) stain), and was negative in all 60 aganglionotic biopsies; these results were reflective of calretinin staining pattern.
  
  
  
  The present study indicates that monoclonal anti-GPC-3 might prove to be useful immunohistochemical marker in the identification of ganglion cells in paraffin-embedded rectal tissue specimens and suction biopsies. Further studies in larger series will contribute to demonstrate its utility as an ancillary marker in the histological assessment of HSCR aganglionosis.
authors.affiliation: *Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua †Division of Pediatric Surgery, Department of Pediatrics Salus Pueri, University of Padova, Padova, Italy.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Ludwig
authors.forename: Andrea
authors.initials: A
authors.lastname: Volpe
authors.forename: Vincenza
authors.initials: V
authors.lastname: Guzzardo
authors.forename: Luisa
authors.initials: L
authors.lastname: Santoro
authors.forename: Paola
authors.initials: P
authors.lastname: Midrio
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Gamba
authors.forename: Rita
authors.initials: R
authors.lastname: Alaggio
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D064032:Calbindin 2 / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D053673:Glypicans / Q000037:antagonists & inhibitors* / Q000276:immunology; D006627:Hirschsprung Disease / Q000473:pathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011237:Predictive Value of Tests; D012007:Rectum / Q000473:pathology; D012189:Retrospective Studies
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D064032:Calbindin 2; C105937:GPC3 protein, human; D053673:Glypicans