Studies of molecular features and novel prognostic biomarkers of cutaneous melanoma

Abstract: Cutaneous malignant melanoma is a highly heterogeneous disease. Immunotherapy has revolutionized the treatment of stage IV disease and is now successfully administered as adjuvant treatment in stage III and soon in stage II. Correct identification of the patients at high risk for progressive disease who will benefit from the treatment is crucial. Important prognostic features in the early phase of the disease are to be found within the primary tumor and sentinel lymph node, but plenty is still to be investigated. Sentinel lymph node biopsy (SLNB) status is one of the independent prognostic factors guiding treatment decisions, but not without controversy. Approximately 80% of the SLNB are negative, contrasting to a wide range of prognosis in node-negative patients. In paper I, we explored the molecular features of melanoma arising in chronic sun-damage skin, proving that this type of melanoma is a distinct molecular entity with a different progression compared to the more common melanoma in intermittently sun-exposed skin. In papers II and III, we evaluated a novel non-invasive prognostic test to be utilized in primary cutaneous melanoma. In our investigation, the CP-GEP test was able to safely identify the patients where the sentinel lymph node biopsy is unnecessary. The same CP-GEP test was able to stratify the patients with high and low risk of disease progression, but the test algorithm still needs to be optimized for this purpose in a clinical setting. In paper IV, we showed that digital quantification of crucial inflammatory cells in the primary tumor microenvironment using immunohistochemistry has a potential to further stratify primary melanoma at risk of brain metastasis.