title: Transcriptional activation of Hedgehog pathway components in aggressive haemangioma.
abstract: Infantile hemangioma is a vascular neoplasm and is one of the most common tumors diagnosed in young children. Although most hemangiomas are harmless and involute spontaneously, some show severe progression, leading to serious complications, such as high-output cardiac failure, ulcerations, compression of the trachea or deprivation amblyopia, depending on their size and localization. However, the pathogenesis and cause of hemangioma are largely unknown to date. The goal of this study was to identify markers that could predict hemangiomas with aggressive growth and severe progression that would benefit from early intervention. By using a PCR-based screening approach, we first confirmed that previously known markers of hemangioma, namely FGF2 and GLUT1, are highly expressed in hemangioma. Nevertheless, these genes did not show any differential expression between severely progressing tumors and mild tumors. However, transcriptional upregulation of several Hedgehog signalling components, comprising the ligand Sonic Hedgehog (SHH), the transcription factor GLI2 and its target gene FOXA2 were detected in extremely aggressive hemangioma specimens during the proliferation phase. Notably, GLI2 was even overexpressed in involuting hemangiomas if they showed an aggressive growth pattern. In conclusion, our data suggest that overexpression of the Hedgehog components SHH, GLI2 and FOXA2 might be used as markers of an aggressive hemangioma that would benefit from too early intervention, while FGF2 and GLUT1 are more general markers of hemangiomas.
authors.affiliation: Department of Pediatric Surgery, Dr. von Hauner Childrens' Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Danielle S
authors.identifier: 0000-0002-0093-5928
authors.initials: DS
authors.lastname: Wendling-Keim
authors.affiliation: Department of Pediatric Surgery, Dr. von Hauner Childrens' Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.|Department of Pediatric Surgery, Klinikum Memmingen, Memmingen, Germany.
authors.forename: Lynn
authors.initials: L
authors.lastname: Wanie
authors.affiliation: Department of Pediatric Surgery, Dr. von Hauner Childrens' Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Dietrich
authors.initials: D
authors.lastname: von Schweinitz
authors.affiliation: Department of Pediatric Surgery, Dr. von Hauner Childrens' Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Grantzow
authors.affiliation: Department of Pediatric Surgery, Dr. von Hauner Childrens' Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Kappler
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D051272:Glucose Transporter Type 1 / Q000235:genetics; D053823:Hedgehog Proteins / Q000235:genetics*; D006391:Hemangioma / Q000235:genetics* / Q000473:pathology; D051542:Hepatocyte Nuclear Factor 3-beta / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009687:Nuclear Proteins / Q000235:genetics*; D012189:Retrospective Studies; D015398:Signal Transduction / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D014158:Transcription, Genetic; D000075746:Zinc Finger Protein Gli2 / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C496502:FOXA2 protein, human; C082593:GLI2 protein, human; D051272:Glucose Transporter Type 1; D053823:Hedgehog Proteins; D009687:Nuclear Proteins; C509239:SHH protein, human; C495677:SLC2A1 protein, human; D000075746:Zinc Finger Protein Gli2; D016222:Fibroblast Growth Factor 2; D051542:Hepatocyte Nuclear Factor 3-beta
keywords: 
  
  SHH
  
  ; 
  FOXA2
  ; 
  GLI2
  ; Hedgehog signalling; infantile hemangioma