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Sonic hedgehog signalling proteins are frequently expressed in retinoblastoma and are associated with aggressive clinicopathological features
  1. Ji-Young Choe1,2,
  2. Ji Yun Yun1,2,
  3. Yoon Kyung Jeon1,3,
  4. Se Hoon Kim4,
  5. Ho-Kyung Choung5,
  6. Sohee Oh6,
  7. Mira Park7,
  8. Ji Eun Kim1,7
  1. 1Department of Pathology, Seoul National University, College of Medicine, Seoul, Korea
  2. 2Department of Pathology, Seoul National University Bundang Hospital, Gyeonggi-Do, Korea
  3. 3Department of Pathology, Seoul National University Hospital, Seoul, Korea
  4. 4Department of Pathology, Yonsei Unversity, College of Medicine, Seoul, Korea
  5. 5Department of Ophthalmology, Seoul National University Boramae Hospital, Seoul, Korea
  6. 6Department of Biostatistics, Seoul National University Boramae Hospital, Seoul, Korea
  7. 7Department of Pathology, Seoul National University Boramae Hospital, Seoul, Korea
  1. Correspondence to Dr Ji Eun Kim, Department of Pathology, Seoul National University Boramae Hospital, 20, Boramae-Ro 5-Gil, Dongjak-Gu, Seoul 110-744, Korea; npol181{at}snu.ac.kr

Abstract

Aims 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.

  • CANCER
  • IMMUNOHISTOCHEMISTRY
  • OPHTHALMOLOGY

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