title: Expressions of sonic hedgehog, patched, smoothened and Gli-1 in human intestinal stromal tumors and their correlation with prognosis.
abstract: OBJECTIVE
  To investigate the role that the hedgehog (Hh) signaling pathway, which includes sonic hedgehog (Shh), Patched (Ptc), Smoothened (Smo) and Gli-1, plays in human gastrointestinal stromal tumors (GISTs).
  
  
  METHODS
  Surgically resected specimens from patients with GISTs, leiomyomas and schwannomas were examined by immunohistochemical staining for aberrant expression of hedgehog signaling components, Shh, Ptc, Smo and Gli-1, respectively.
  
  
  RESULTS
  In GISTs, 58.1% (18 of 31), 77.4% (24 of 31), 80.6% (25 of 31) and 58.1% (18 of 31) of the specimens stained positive for Shh, Ptc, Smo and Gli-1, respectively. In leiomyomas, 92.3% (12 of 13), 92.3% (12 of 13), 69.2% (9 of 13) and 92.3% (12 of 13) stained positive for Shh, Ptc, Smo and Gli-1, respectively. In schwannomas, 83.3% (5 of 6), 83.3% (5 of 6), 83.3% (5 of 6) and 100% (6 of 6) stained positive for Shh, Ptc, Smo and Gli-1, respectively. Immunohistochemistry revealed that the expressions of Shh and Gli-1 were significantly higher in leiomyomas than in GISTs (P < 0.05, respectively). Shh expression strongly correlated with the grade of tumor risk category and with tumor size (P < 0.05, respectively). However, the expressions of Ptc and Smo did not correlate with histopathological differentiation.
  
  
  CONCLUSIONS
  These results suggest that the Hh signaling pathway may play an important role in myogenic differentiation and the malignant potential of human intestinal stromal tumors.
authors.affiliation: Department of Molecular Pathology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Yoshizaki
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nakayama
authors.forename: Shinji
authors.initials: S
authors.lastname: Naito
authors.forename: Chun-Yang
authors.initials: CY
authors.lastname: Wen
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sekine
mesh_terms: D002471:Cell Transformation, Neoplastic; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007414:Intestinal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007889:Leiomyoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009442:Neurilemmoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000072079:Patched Receptors; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D000072086:Smoothened Receptor; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1
chemical_list: C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C509239:SHH protein, human; C491023:SMO protein, human; D000072086:Smoothened Receptor; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D004815:Epidermal Growth Factor; D011505:Protein-Tyrosine Kinases