Validation of Ambra-1 and Loricrin as prognostic biomarkers for the early detection of high risk melanomas
This is a technical overview of the Newcastle University research group’s project that has been selected for funding by Melanoma Focus within the charity’s Patient Impact Programme. For further information about the award click here.
This study aims to validate the immunohistochemical expression of epidermal Ambra-1 and loricrin in a statistically powered cohort of primary melanomas as biomarkers to identify high risk tumours currently mis-diagnosed in terms of disease prognosis under current AJCC staging criteria.
Following diagnosis with melanoma, patient prognosis is presently based on clinico-pathological criteria within the primary tumour. Although robust, AJCC staging criteria can only broadly categorise risk of disease progression based on epidemiological data from cohorts of other patients with similar staging in prior clinical reviews.
Currently, patients with thin melanomas are categorised as AJCC stage Ia/b, and considered as being at a low risk of metastasis. However, 10% of AJCC Ia/b patients develop distant disease, and as such are mis-diagnosed on the basis of current disease stratification. The ability to stratify this group of seemingly ‘low-risk’ patients more accurately would have a major impact on patient follow-up, the intensity of investigation, and the instigation of targeted adjuvant therapies in a trial or therapeutic setting.
Improved stratification of early melanoma would increase clinician confidence in the explanation of likely disease outcome, allowing patients to plan for their future treatment appropriately and reduce the psychological burden of the uncertainty around current staging in early disease.
We will delineate the association of increased TGFβ2 secretion by primary melanomas with resultant down regulation of peri-tumoural Ambra-1 and loricrin, as key events in the development of tumour ulceration and eventual metastasis.
Results will inform the development of novel therapeutics targeting TGFβ2 in high risk melanoma patients as identified by peri-tumoural epidermal Ambra-1 and loricrin expression, thus reducing overall disease mortality.