title: Sonic hedgehog signalling proteins are frequently expressed in retinoblastoma and are associated with aggressive clinicopathological features.
abstract: OBJECTIVE
  This study aimed to examine the expression of Sonic hedgehog (SHH) signalling proteins in retinoblastoma and to evaluate its clinical significance.
  
  
  METHODS
  Seventy-nine enucleated retinoblastoma tumours were investigated immunohistochemically using antibodies against SHH pathway proteins, such as SHH, glioma-associated oncogene homologue (GLI) 1, GLI2, GLI3 and ABC binding cassette G2 (ABCG2). Western blotting of SHH signalling proteins was performed in two retinoblastoma cell lines.
  
  
  RESULTS
  SHH was expressed in most retinoblastoma cases (78 of 79, 98.7%), with 21 cases (26.6%) showing strong expression. GLI1 and GLI2 were also frequently expressed: 67 of 78 cases (85.9%) and 71 of 77 cases (92.2%), respectively. GLI3, a transcriptional repressor, was expressed at low levels in 23 of the 78 cases (29.5%). High ABCG2 expression was found in 23 of the 78 cases (29.5%). High expression levels of these proteins in retinoblastoma cell lines were confirmed by western blotting. The expression of SHH was associated with advanced stages, local invasion and metastasis (all p<0.05).
  
  
  CONCLUSIONS
  SHH signalling molecules were frequently expressed in retinoblastoma tumour cells, and high SHH expression was closely related to an advanced disease status. Our results suggest that the SHH signalling pathway may play a role in the progression of retinoblastoma.
authors.affiliation: Department of Pathology, Seoul National University, College of Medicine, Seoul, Korea Department of Pathology, Seoul National University Bundang Hospital, Gyeonggi-Do, Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Choe
authors.affiliation: Department of Pathology, Seoul National University, College of Medicine, Seoul, Korea Department of Pathology, Seoul National University Bundang Hospital, Gyeonggi-Do, Korea.
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Yun
authors.affiliation: Department of Pathology, Seoul National University, College of Medicine, Seoul, Korea Department of Pathology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
authors.affiliation: Department of Pathology, Yonsei Unversity, College of Medicine, Seoul, Korea.
authors.forename: Se Hoon
authors.identifier: http://orcid.org/0000-0001-7516-7372
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Seoul National University Boramae Hospital, Seoul, Korea.
authors.forename: Ho-Kyung
authors.initials: HK
authors.lastname: Choung
authors.affiliation: Department of Biostatistics, Seoul National University Boramae Hospital, Seoul, Korea.
authors.forename: Sohee
authors.initials: S
authors.lastname: Oh
authors.affiliation: Department of Pathology, Seoul National University Boramae Hospital, Seoul, Korea.
authors.forename: Mira
authors.initials: M
authors.lastname: Park
authors.affiliation: Department of Pathology, Seoul National University, College of Medicine, Seoul, Korea Department of Pathology, Seoul National University Boramae Hospital, Seoul, Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Kim
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D002675:Child, Preschool; D005260:Female; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D012175:Retinoblastoma / Q000378:metabolism* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D053823:Hedgehog Proteins
keywords: CANCER; IMMUNOHISTOCHEMISTRY; OPHTHALMOLOGY