title: A high-throughput study in melanoma identifies epithelial-mesenchymal transition as a major determinant of metastasis.
abstract: Metastatic disease is the primary cause of death in cutaneous malignant melanoma (CMM) patients. To understand the mechanisms of CMM metastasis and identify potential predictive markers, we analyzed gene-expression profiles of 34 vertical growth phase melanoma cases using cDNA microarrays. All patients had a minimum follow-up of 36 months. Twenty-one cases developed nodal metastatic disease and 13 did not. Comparison of gene expression profiling of metastatic and nonmetastatic melanoma cases identified 243 genes with a >2-fold differential expression ratio and a false discovery rate of <0.2 (206 up-regulated and 37 down-regulated). This set of genes included molecules involved in cell cycle and apoptosis regulation, epithelial-mesenchymal transition (EMT), signal transduction, nucleic acid binding and transcription, protein synthesis and degradation, metabolism, and a specific group of melanoma- and neural-related proteins. Validation of these expression data in an independent series of melanomas using tissue microarrays confirmed that the expression of a set of proteins included in the EMT group (N-cadherin, osteopontin, and SPARC/osteonectin) were significantly associated with metastasis development. Our results suggest that EMT-related genes contribute to the promotion of the metastatic phenotype in primary CMM by supporting specific adhesive, invasive, and migratory properties. These data give a better understanding of the biology of this aggressive tumor and may provide new prognostic and patient stratification markers in addition to potential therapeutic targets.
authors.affiliation: Molecular Pathology Programme and Histology and Immunohistochemistry Unit, Centro Nacional de Investigaciones Oncológicas, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Soledad R
authors.initials: SR
authors.lastname: Alonso
authors.forename: Lorraine
authors.initials: L
authors.lastname: Tracey
authors.forename: Pablo
authors.initials: P
authors.lastname: Ortiz
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pérez-Gómez
authors.forename: José
authors.initials: J
authors.lastname: Palacios
authors.forename: Marina
authors.initials: M
authors.lastname: Pollán
authors.forename: Juan
authors.initials: J
authors.lastname: Linares
authors.forename: Salvio
authors.initials: S
authors.lastname: Serrano
authors.forename: Ana I
authors.initials: AI
authors.lastname: Sáez-Castillo
authors.forename: Lydia
authors.initials: L
authors.lastname: Sánchez
authors.forename: Raquel
authors.initials: R
authors.lastname: Pajares
authors.forename: Abel
authors.initials: A
authors.lastname: Sánchez-Aguilera
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Artiga
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Piris
authors.forename: José L
authors.initials: JL
authors.lastname: Rodríguez-Peralto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000556:secondary*; D008648:Mesoderm / Q000473:pathology; D008875:Middle Aged; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology* / Q000556:secondary*