April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Analysis of the Hedgehog signalling pathway in periocular sebaceous gland carcinoma
Author Affiliations & Notes
  • John Bladen
    Centre for Cutaneous Research, Barts & The London School of Medicine, London, United Kingdom
    Adnexal Oncology, Moorfields Eye Hospital, London, United Kingdom
  • Caroline Thaung
    Pathology, UCL Institute of Ophthalmology, London, United Kingdom
  • Michele Beaconsfield
    Adnexal Oncology, Moorfields Eye Hospital, London, United Kingdom
  • Edel O’Toole
    Centre for Cutaneous Research, Barts & The London School of Medicine, London, United Kingdom
  • Michael Philpott
    Centre for Cutaneous Research, Barts & The London School of Medicine, London, United Kingdom
  • Footnotes
    Commercial Relationships John Bladen, None; Caroline Thaung, None; Michele Beaconsfield, None; Edel O’Toole, None; Michael Philpott, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1282. doi:
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      John Bladen, Caroline Thaung, Michele Beaconsfield, Edel O’Toole, Michael Philpott; Analysis of the Hedgehog signalling pathway in periocular sebaceous gland carcinoma. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1282.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Sebaceous gland carcinoma (SGC) is a masquerader of benign conditions leading to significant eye morbidity, including destructive surgical treatment such as exenteration, and mortality in up to 22% of patients. Little is known about the genetic or molecular basis of SGC. Aberrant Hedgehog (Hh) signalling has been implicated, however, the pathway has not been assessed in detail. In contrast, basal cell carcinoma (BCC) is known to involve the Hh pathway, often through mutational inactivation of the Patched-1 (PTCH1) gene. This makes BCC a good tumour for comparison of abnormal Hh activation. The aim is to identify any canonical Hh pathway aberrance in SGC along with its magnitude by comparing it directly to nodular BCC.

Methods: Periocular SGC and nodular BCC tissue were obtained from the Moorfields Biobank; SGC (n=15) samples were compared to nodular BCC (n=10) and control tissue (testes, n=4). Expression of PTCH1, Smoothened (SMO), and Glioblastoma transcription factors (GLI1 and GLI2) were assessed in histological sections using immunohistochemistry and immunofluorescence techniques. Semi-quantification was carried out comparing tumours and control tissue using Image J.

Results: Upregulation of the canonical Hh signalling pathway in SGC was demonstrated by overexpression of PTCH1, SMO, GLI1 and GLI2 compared to nodular BCC and control tissue.

Conclusions: The Hh signalling pathway is significantly more upregulated in periocular SGC compared to nodular BCC, a known aberrant Hh pathway tumour. This raises the possibility of potential treatment targets that are already in clinical practice (such as SMO antagonists) to avoid or reduce destructive surgical treatment, preserve vision and prevent mortality.

Keywords: 624 oncology • 554 immunohistochemistry • 744 tumors  
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