FAQs for Clinicians

For clinicians interested in
the AMBRA1 and loricrin Referral Service

The following FAQs are designed to answer the questions of doctors, dermatologists and other clinicians. If you are a patient, please see your dedicated FAQs here.

Which type of melanoma is suitable for the test?

Non-ulcerated melanomas staged as IA, IB, IIA and IIB have been shown to be responsive to the AMBRA1 and loricrin antibodies.

Who can order the test?

The test can only be ordered by a doctor as they need to ask the pathology department to prepare the tissue slides.

How do I order the test?

Download the Test Referral Form (TRF), complete it and send to pathology.

How much does the test cost?

The charge from AMLo to the patient is £293, excluding VAT. This does not include any pathology services for the trust to prepare and send the samples to CellPath.

Does the patient have to pay for the test?

Currently the NHS does not routinely fund the AMBRA1 and loricrin test. Either seek NHS funding or the patient will have to contact AMLo Biosciences to pay for the test.

How does the patient pay for the test?

The test is still very new so until a dedicated payment system is established, the patient will need to contact AMLo directly at referral@amlo-biosciences.com, or call us on 0191 580 7180. We will take the patient’s details and issue an invoice for the test at the appropriate time.

How long does the test take?

After the dermatologist has confirmed the need for the test with pathology, the pathology team will need to send 5 x 4-micron sections of the melanoma to CellPath in Newcastle. From the point of receiving the sample CellPath will report the result back to the requesting clinician within 3–5 working days.

Can a patient order the test without a doctor's consent?

No, the test needs to be conducted with the doctor’s consent.

To whom will the test results go?

The test results will be sent from CellPath at Newcastle Hospitals to the referring clinician by secure email.

Does the NHS fund the test?

At present the AMBRA1 and loricrin test is not routinely funded by the NHS. Individual doctors will need to make the request for special case funding or make a business case request to their hospital.

Do private insurers fund the test?

At present the test is not routinely funded by private insurers. Individual doctors will need to make the request for special case funding to the patient’s insurer. AMLo is working with private providers so watch the website for updates.

Does the NHS routinely use the test?

The AMBRA1 and loricrin test is very new and so it has not yet been adopted into routine NHS practice. Watch the websites for updates.

Which bodies in the UK have approved/reviewed the test?

The AMBRA1 and loricrin test has been approved for use at CellPath by UKAS through their validation process.

Can the patient have the test if pathology has not retained enough of the original melanoma biopsy?

Sometimes melanomas are very small indeed and all the tissue is used for the diagnosis and staging. The test uses very little extra tissue but on rare occasions there isn’t enough to stain. In this case the patient will be unable to have the AMBRA1 and loricrin test but many melanomas that are taken away completely do not progress to advanced disease.

Melanoma diagnosis occurred several years ago. Can the test still be conducted?

As long as enough tissue has been retained, the test can be conducted. However, for Stage IA diagnoses the standard follow up is 1–2 years and so AMLo only recommends retrospective use of AMBRA1 and loricrin on Stage IA melanomas of less than 2 years since diagnosis. For melanomas that were staged as IB, IIA or IIB the standard follow up is 5 years and so AMBRA1 and loricrin could be used on this stage of melanoma for up to 5 years post diagnosis.

What do the test results mean?

Melanoma will progress if left in situ. Fortunately most early-stage melanomas have a successful excision. However, at the point of removal it isn’t currently possible to predict who will and will not develop metastatic disease. That is why, currently, up to 15% of people with Stage I and II melanoma will progress despite excision.

AMBRA1 and loricrin are proteins naturally occurring in the skin and their presence or absence can be used to accurately predict who is truly at low risk of progression. Data suggests that this could be between 17–62% of patients

References

Ellis R, et al. Br J Dermatol. 2020;182(1):156–65.

Ewen, Poster, SMR Congress 2021 (PDF download)

What is your recommendation for reduced follow-up?

The current NICE Guidance on Melanoma NG14 was published in 2015 and will be updated in 2022. The current recommendation for follow-up by stage in the UK is:

  • Stage IA: 2–4 visits in year 1
  • Stages IB–IIB: 4 visits per year for 3 years and then 2 visits each in years 4 & 5

After a low-risk AMBRA1 and loricrin result we suggest the following step-down change in surveillance. However, other risk factors should be taken into account before implementing step-down:

  • Stage IA: just 1 visit after 12 months
  • Stage IB-IIB: 1 visit per year for 4 years

How accurate is the test?

The antibodies to AMBRA 1 and loricrin have been tested on retrospective melanoma biopsies with up to 10 years clinical follow-up. They have now been validated in over 750 patients from UK, USA, Australia and Spain. The latest data set in over 400 Stage I and II melanomas demonstrated an NPV of 97.1% and sensitivity of 95.7% meaning that AMBRA1 and loricrin is very effective at identifying melanomas that are truly low risk. Please see website for further scientific data.

Can the test be performed on an acral malignant melanoma?

No, melanomas arising at these sites cannot be tested.

Can the test be performed on sino-nasal, oral, conjunctival, female genital or ocular melanomas?

No, melanomas arising at these sites cannot be tested.

Can the test be performed on shave and punch biopsies?

An excision with surrounding marginal skin is ideal but the AMBRA1 and loricrin test can be performed on shave and punch biopsies using a normal skin positive control.

Can the test be performed on patients with a genetic tendency to develop melanomas?

Such patients should be excluded from testing as they will require intense follow-up regardless.

Can desmoplastic melanoma be tested by AMBRA1 and loricrin?

Yes.

Can AMBRA1 and loricrin be used if the patient has a co-existing inflammatory disorder or hereditary skin disorder?

Yes, provided the melanoma has not arisen in an abnormal skin lesion.

Will any unstained sections that are sent to AMLo be used or will they be destroyed, returned or retained?

The sections used for the test will be retained in the pathology archive, under a Human Tissue Authority licence. Any unused sections will be destroyed.

If the AMLo pathologist disagrees with the information in the original pathology report, what will happen?

The histopathologist undertaking the test will get in touch with the reporting pathologist to discuss any questions that may arise.

If the test is negative/at-risk, are there any alternative tests that might be helpful?

Currently there are no guidelines to advise about this. The current NICE NG14 Melanoma Management suggests sentinel lymph node biopsies for clinically relevant lesions. These are usually those over 1mm in depth.

Does the test work on types of skin cancer other than melanoma?

This is under investigation but testing on other cancers cannot be offered at present.

I see from the test result that only one of the markers is retained. Is that sufficient for a positive result?

Yes, retaining just one of loricrin or AMBRA1 is still a positive/low-risk result.

Why does retention of AMBRA1 and/or Loricrin indicate a low risk?

Melanomas at risk of spreading secrete a particular form of TGFβ—called TGFβ2—which causes reduction of these proteins in the epidermis over the melanoma.

Reference

Cosgarea I, et al. https://onlinelibrary.wiley.com/doi/10.1111/bjd.20889

What do I do if a patient presents with more than one melanoma?

First of all determine if the melanomas are two primaries or a primary and secondary metastasis. If there are two primaries then order an AMBRA 1 and loricrin test for each primary. If the second melanoma is a metastasis, then the primary is already classified as being high risk and the test will not add any useful information to the management of the patient.

Why is the test not available as a blood test?

The test uses the tissue taken during the initial biopsy or later wide layer excision. It is applied to this tissue to enable a pathologist to examine the melanoma and surrounding healthy skin under the microscope. No further surgery is required.

I am not in the UK. Can I order the test?

Sorry, the test is currently only available in the UK.

Job code: 2021/AMBLor/UK/0023
Date of preparation: October 2021

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Trading address: Office 9, The Biosphere, Drayman's Way, Newcastle Helix, Newcastle upon Tyne, NE4 5BX

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