Overview
The eyelid is a common site for skin cancer. Most of these tumours are ‘basal cell carcinomas’ and about 1 in 20 are sebaceous gland carcinomas.
Basal cell carcinomas are unlikely to spread, but there is an aggressive subtype that invades tissue in the nose and eye socket. Sebaceous gland carcinoma is more likely to spread and can be fatal for about 1 in 5 people affected.
Both conditions can lead to significant eye damage, from the cancer itself and from surgical treatment. Sometimes the whole eye has to be removed, causing blindness.
We don’t know much yet about what causes these cancers or how they develop. So the aim of this project is to try to find out why they spread so easily and aggressively through the skin.
Mr Bladen is developing 3D models with cells taken from these tumours and is looking at how cells multiply. He is also comparing behaviour between the more and less aggressive cancers. The aim is to learn more about how these cancers work and also to find any relevant genes and targets for treatment.
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Scientific summary
Identification of genetic factors involved in morphoeic basal cell (mBCC) and sebaceous gland carcinoma (SGC) of human eyelid tumours with a view to identifying potential treatment targets.
Non-melanoma skin cancers (NMSC) are the most common human cancers with rising incidence. Morphoeic basal cell carcinoma (mBCC) and sebaceous gland carcinoma (SGC) are two aggressive subtypes of eyelid NMSC, but little is known about their aetiology. This project aims to dissect the molecular basis of aggressive eyelid mBCC and SGC through comparison with benign nodular BCC (nBCC), with a view to finding novel therapeutic targets using a stepwise approach.
Fresh human eyelid BCC and SGC tissue samples are being used to generate cell lines and 3D organotypic models of keratinocytes and fibroblasts to understand the migration and invasion of these tumours. Immunohistochemistry and immunofluorescence studies for Sonic Hedgehog (SHH) and epidermal growth factor receptor (EGFR) signalling genes, including GLI, SMO, PTCH, pEGFR, pMEK and phospho-ERK, are being performed on 30 mBCC, SGC and nBCC tissue specimens to determine any differences between the cancers. Modified PTCH knockdown in keratinocytes and fibroblasts are being undertaken to investigate invasion, and correlate GLI expression with EGFR-ERK signalling in the disparate tumours.
Genomic DNA extracted from tissue samples is undergoing next generation sequencing and micro- and phospho- arrays to determine the global genetic mutational profile of these eyelid tumours. Through these experiments, a better understanding of SHH and EGFR signalling will be reached on the invasive and migratory properties of mBCC and SGC. Therapeutic strategies may be elucidated to reduce cancer invasion, avoid destructive eyelid surgery and importantly prevent mortality.