What is the AMBLor test?

When a melanoma is removed surgically from the skin, the cellular make-up of the tumour is analysed microscopically by a histopathologist. They use a process called immunohistochemistry to stain the cells various colours (usually blue and pink) to allow them to identify different cell types such as melanoma cells, epidermal cells or white blood cells. As part of this process, the AMBLor test can be used to identify two proteins, AMBRA1 and loricrin, in the top layer of the skin (epidermis). It has been shown that when AMBLor protein levels in the epidermis over the melanoma are less than the levels within the normal epidermis away from the melanoma, it is more likely for the melanoma to spread to other parts of the body (metastases) at which point it can become potentially life-threatening.

I have just been diagnosed with a melanoma, how can I get the AMBLor test?

The AMBLor test is only available in a research setting currently, which means it’s not generally available at present. We hope that following completion of upcoming studies, the AMBLor test will become part of various melanoma treatment guidelines. The antibodies that are used in the test have also recently been developed; as such, these need to undergo various batches of testing over a 12-month period before they can be used for clinical management decisions.

In future, we would expect that the local histopathology team at your treatment Hospital will send sections of your melanoma specimen for analysis of the AMBLor test at our facility within Newcastle University.

How can I be sure that the test is accurate?

To date, the AMBLor test has been undertaken in over 500 patients, with up to 14 years of follow-up data. The vast majority of these patients have AJCC stage Ia melanomas, but we have also tested AJCC stage II melanomas also. We have used a very rigorous, “blinded” process in which the clinician scoring the samples was unaware of whether the melanoma did progress to other parts of the body or not. Our most important finding to date, is that when a patient is given a “low risk” AMBLor score there is a 98.8% chance of this being correct i.e. that the tumour does not spread to other parts of the body.

Where and how was the test developed?

The AMBLor biomarker was developed in Prof Penny Lovat’s laboratory within the Institute of Cellular Medicine, Newcastle University. Prof Lovat has been working in the field of melanoma biology, with particular interest in a process called autophagy for over a decade, and continues to be a leading figure in translational research; essentially, identifying new discoveries in melanoma science and developing them into practical investigations or treatments for clinical usage.

Prof Lovat’s team received an award for £100,000 to develop the AMBLor test from the Melanoma Focus Group which was able to kickstart the project

How do I find out if the test is appropriate for me?

At present, the AMBLor test is purely for research purposes only. Once we have accrued further evidence of its potential benefit to melanoma patients, we hope that it will form part of many international guidelines for the appropriate management of melanoma patients. As part of the development of the biomarker, we have also had to make our own antibodies which are much more accurate than those available currently. This will allow them to be of an appropriate quality to use in a clinical setting. The process requires at least 12 months of testing of the antibodies which should be completed towards the end of 2019.

Although most of our data to date has been in AJCC stage I a melanomas, we feel that it is likely to be of value in assessing all primary melanoma samples as long as the tumours are not ulcerated.

I have been told my melanoma is ulcerated; what does this mean?

An ulcer is defined as an area with a loss of the epidermis which is the top layer of the skin. Melanomas, normally develop at the junction between the epidermis and dermis; and as they mature, they tend to penetrate further into the dermis. As part of this process, some melanomas lose the epidermis overlying them. The reason for this has been poorly understood previously. We feel, however, that it is related to something being secreted by the melanomas which interacts with AMBRA1 in the epidermis, leading eventually to ulceration.

As the AMBLor test reveals changes of proteins within the epidermis, if the tumour is ulcerated these proteins cannot be visualised which makes the test inaccurate in ulcerated tumours. For this reason, the AMBLor test cannot be undertaken in ulcerated melanomas.

Can I only have the test at diagnosis of my melanoma?

Although identifying the risk of disease progression as accurately as possible at the time of diagnosis, we know that melanomas can spread to other parts of the body sometimes over a decade after initial diagnosis. The AMLo team therefore feel that the use of the AMBLor marker would still be of benefit to patients potentially many years after diagnosis to help diminish some of the uncertainties around the current AJCC scoring system of melanoma.

Can I ask for the AMBLor test to be done directly from the company?

Although we hope that the AMBLor test will become a standard of practice for melanoma care within the UK, thus meeting the test free for all newly-diagnosed melanoma patients, this may not include patients who have previously been diagnosed with the condition. As part of the development of the biomarker we hope to be able to offer the test directly to patients previously diagnosed with melanoma. Unfortunately, this is unlikely to be covered by the NHS and so must be purchased directly by an individual. If this is of interest to you, please keep an eye on the website where we will update the availability of this test regularly.

If the test says that I am “low risk”, what is the chance it could be wrong?

One of the main strengths of the AMBLor test is that it has a high negative predictive value. This essentially means that if the test identifies an individual as “low risk” it is very unlikely that the disease will progress. So far, our results from four patient cohorts suggest that the chance of a melanoma spreading to other parts of the body following an AMBLor “low risk” result is around 2%. This compares favourably with the AJCC staging which suggest that up to 10% of melanomas diagnosed as stage I will progress.

My doctor wants me to have regular follow-ups, but if the test says I’m low risk would this still happen?

Although we are confident in the accuracy of the AMBLor biomarker at helping to further predict a patient’s risk of disease progression, its position in the normal treatment regime of a melanoma patient has yet to be decided.

The AMLo team are in discussion with the National Institute of Clinical Excellence (NICE) to see how we can make this test available for all patients diagnosed with melanoma in the UK. As part of this, we are also undertaking a National Institute of Health Research sponsored health technology assessment looking at the current evidence base for follow-up regimes in patients diagnosed with stage I melanoma. This will allow us to design evidence-based follow-up regimes for the future, as well as assessing what role the AMBLor test may have in future treatment decisions. It may be, if a patient has a “low risk” AMBLor result, that they undergo a less rigorous follow-up regime, but this will be decided on by the expert advisory groups who produce the melanoma guidelines for the UK.

Do I need to have a further procedure undertaken for the AMBLor test to be undertaken?

No. The test is undertaken on the primary melanoma samples taken at the time of surgical removal of the lesion. Normally, these samples are placed in blocks of wax and then very fine sections are taken through the tumour and placed on slides for analysis. We only require six sections for the test, which still equates to an area of the tumour thinner than a human hair!

AMLo Biosciences Limited is a company registered in England and Wales. Company # 11004534

Trading address: Newcastle University, The Medical School, Framlington Place, Newcastle upon Tyne, NE2 4HH, United Kingdom

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