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Graefe's Archive for Clinical and Experimental Ophthalmology

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Open Access 01-04-2018 | Oncology

Analysis of hedgehog signaling in periocular sebaceous carcinoma

Authors: John C. Bladen, Mariya Moosajee, Dhani Tracey-White, Michèle Beaconsfield, Edel A. O’Toole, Michael P. Philpott

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 4/2018

Abstract

Purpose

Sebaceous carcinoma (SC) is a clinical masquerader of benign conditions resulting in significant eye morbidity, sometimes leading to extensive surgical treatment including exenteration, and even mortality. Little is known about the genetic or molecular basis of SC. This study identifies the involvement of Hedgehog (Hh) signaling in periocular SC.

Methods

Fifteen patients with periocular SC patients were compared to 15 patients with eyelid nodular basal cell carcinoma (nBCC; a known Hh tumor), alongside four normal individuals as a control for physiological Hh expression. Expression of Patched 1 (PTCH1), Smoothened (SMO), and glioma-associated zinc transcription factors (Gli1 and Gli2) were assessed in histological sections using immunohistochemistry and immunofluorescence (IF) techniques. Antibody specificity was verified using Western-blot analysis of a Gli1 over-expressed cancer cell line, LNCaP-Gli1. Semi-quantification compared tumors and control tissue using IF analysis by ImageJ software.

Results

Expression of the Hh pathway was observed in SC for all four major components of the pathway. PTCH1, SMO, and Gli2 were more significantly upregulated in SC (P < 0.01) compared to nBCC. Stromal expression of PTCH1 and Gli2 was observed in SC (P < 0.01). In contrast, stromal expression of these proteins in nBCC was similar or down-regulated compared to physiological Hh controls.

Conclusions

The Hh signaling pathway is significantly more upregulated in periocular SC compared to nBCC, a known aberrant Hh pathway tumor. Furthermore, the stroma of the SC demonstrated Hh upregulation, in particular Gli2, compared to nBCC. Targeting of this pathway may be a potential treatment strategy for SC.

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Title: Analysis of hedgehog signaling in periocular sebaceous carcinoma
Authors: John C. Bladen
Mariya Moosajee
Dhani Tracey-White
Michèle Beaconsfield
Edel A. O’Toole
Michael P. Philpott
Publication date: 01-04-2018
Publisher: Springer Berlin Heidelberg
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 4/2018
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-018-3900-5

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Analysis of hedgehog signaling in periocular sebaceous carcinoma

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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