FAQs for Clinicians

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

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.

The test is still very new so until a dedicated payment system is established, the patient will need to contact AMLo directly at [email protected], 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.

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

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

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

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.

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.

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)

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

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.

No, melanomas arising at these sites cannot be tested.

No, melanomas arising at these sites cannot be tested.

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.

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

Yes.

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

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.

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

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.

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

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

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

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.

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.