The Mol-Mel study will focus on different tasks and for each task different investigations will be carried out:
* Standardization and tissue quality control: The quality of the samples will then be determined using hematoxylin \& eosin (HE)-staining. If any quality issue is detected feedback will be sent to the clinical center responsible for providing the sample
* Histopathology \& computational pathology: Melanoma samples will undergo a central pathology review and analysis of conventional prognostic staging parameters. Diagnostically challenging neoplasms will be included in an "inter-observer agreement" carried out by different pathologist.Melanoma samples will also be charactered by single and multi-plex IHC in whole sections and tissue microarrays (TMA), and subjected to automated digital quantification. Spatial proteomics by automated ultra-high content imaging/MACSima Imaging Cyclic Staining (MICS) technology enables simultaneous analysis of hundreds of marker antigens on a single sample. Hundreds of antigens for single sample will be analysed via "Automated ultra-high content imaging/MACSima Imaging Cyclic Staining" (MICS) that will be performed on the novel automated ultra-high content imaging platform MACSimaTM (Miltenyi Biotec).
* Comprehensive somatic, transcriptional and DNA methylation landscape and data integration: DNA and RNA will be extracted by FFPE melanoma samples and characterized using whole-exome sequencing (WES), single nucleotide polymorphism (SNP) and RNA sequencing (RNAseq) arrays on matched tumor/normal pairs of samples. Then recurrent somatic aberrations, DNA methylation subclasses and patterns of tumor evolution will be characterized.
* Pan-European digital second opinion platform: this last task will focus on creating a pan-european second opinion platofrom in order to facilitate standardization of melanoma diagnosis and to share knowledge about biomarkers, algorithms and subtype classification.
