Validation of Ambra-1 and Loricrin as prognostic biomarkers for the early detection of high-risk melanomas
Dr Rob Ellis, The James Cook University Hospital, Middlesbrough and Institute of Cellular Medicine, Newcastle University
Professor Penny Lovat, Institute of Cellular Medicine, Newcastle University
Dr Marie Labus, Business Development Manager, Research and Enterprise Services, Newcastle University
If melanoma spreads (or ‘metastasises’) from the skin to other parts of the body, the prognosis or likelihood of recovery will be affected. Thankfully, most patients can be cured if their melanomas are surgically removed from the skin before this happens. Analysing melanomas after their removal can help clinicians predict which patients remain likely to develop metastatic disease. Currently the accuracy of using this method for prognosis is not exact.
Loss of the surface layer of the skin over a melanoma is known as ulceration. Patients whose melanomas become ulcerated have a worse outcome, but the exact reason for this is unclear. In an initial group of melanoma patients, it was shown that the loss of two proteins, Ambra-1 and loricrin, in this skin layer is linked to the development of ulceration, and a greater risk of the disease spreading.
This research project looked for changes in these two proteins in the ulcerated skin layer of melanomas from a large group of patients. The aim was to find out how to predict which patients are at a higher risk of metastatic melanoma, and who will therefore need to be followed up more closely by clinicians after surgery.
The researchers gained a better understanding of the link between these proteins and skin ulceration, as well as their relationship with another protein, known as transforming growth factor beta-2 (TGFβ2). TGFβ2 is linked to how cells in the body grow and divide and is found in melanomas. Gaining understanding of these proteins may help to develop new treatments for patients who are identified as being at higher risk of disease spread.
Discovering earlier and more effective therapies would reduce the rate of metastasis and overall mortality from this most serious form of skin cancer.
Comment from Principal Investigators
“We are extremely delighted to receive this award as we feel that the results we have seen in a previous cohort of patients, as well as multiple laboratory experiments, suggests that we may have begun to unravel the enigma of melanoma ulceration. In doing so, we have identified two proteins in the epidermis overlying melanomas that when lost in the early stages of melanoma development suggest that a patient is at high risk of disease spread and higher mortality.
By further understanding this process, we may be able to develop new drug treatments to prevent the spread of disease and so impact greatly on the mortality from the condition.
The support of the Melanoma Focus has enabled us to take this project forward, allowing potential patient benefit as soon as possible”
The project resulted in the first melanoma test to identify those at low risk of cancer spreading.
By applying the test – called AMBLor® – to the standard biopsy of the primary melanoma on its removal, patients who are at low risk of the disease reoccurring or spreading can be identified. Melanoma Focus are delighted to fund the initial research that developed this test – which may change the follow-up pathways for patients with stage 1a-2b melanomas.
The effectiveness of the AMLo test is yet to be fully evaluated by the NHS, BAD and NICE. However, if endorsed, this test may be offered to early-stage melanoma patients to potentially reduce the need for some follow-up which will be great news for patients.