Naevi, dysplastic naevi, melanoma in situ, and minimally invasive melanoma: insights and opportunities using proteomic profiling of formalin-fixed and paraffin-embedded tissue and scarless samples

Abstract

Melanoma and benign pigmented lesions have overlapping features which make their diagnosis difficult. As such, discrepancies have resulted in a rise in unnecessary biopsies and excisions as well as clinical and pathological overdiagnosis. There is a demand to improve understanding of melanoma progression especially in early stages when melanoma can be confused with benign lesions. This thesis is a first to investigate the proteome profile of benign naevi, dysplastic naevi, melanoma in situ, and minimally invasive melanoma using data-independent acquisition mass spectrometry analysis of formalin-fixed and paraffin-embedded (FFPE) as well as non-invasively collected (scarless) skin samples. This thesis describes several proteomic signatures that should be further explored as biomarkers for pigmented lesion classification and melanoma diagnosis in FFPE. Furthermore, promising signatures in scarless samples can be used for the non-invasive diagnosis of pigmented lesions and melanoma. Bioinformatic analysis revealed proteins involved in several tumour related functions including tumour cell proliferation and invasion, tumour microenvironment and immune related pathways such as inflammation and integrin signalling. Altogether, this thesis demonstrates FFPE and scarless samples as promising and valuable resources for novel proteomic investigations. My findings provide potential proteins which may have implications in pigmented lesions’ behaviour and cancer related mechanisms and presents proteomic signatures for further exploration and validation in independent cohorts for biomarker adoption into the clinical setting. This will help to reduce the number needed to biopsy and improve melanoma diagnosis.