title: The clinicopathological and gene expression patterns associated with ulceration of primary melanoma.
abstract: Ulceration of primary melanomas is associated with poor prognosis yet is reported to predict benefit from adjuvant interferon. To better understand the biological processes involved, clinicopathological factors associated with ulceration were determined in 1804 patients. From this cohort, 348 primary tumor blocks were sampled to generate gene expression data using a 502-gene cancer panel and 195 blocks were used for immunohistochemistry to detect macrophage infiltration and vessel density. Gene expression results were validated using a whole genome array in two independent sample sets. Ulceration of primary melanomas was associated with more proliferative tumors, tumor vessel invasion, and increased microvessel density. Infiltration of tumors with greater number of macrophages and gene expression pathways associated with wound healing and up-regulation of pro-inflammatory cytokines suggests that ulceration is associated with tumor-related inflammation. The relative benefit from interferon reported in patients with ulcerated tumors may reflect modification of signaling pathways involved in inflammation.
authors.affiliation: Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
authors.forename: Rosalyn
authors.initials: R
authors.lastname: Jewell
authors.forename: Faye
authors.initials: F
authors.lastname: Elliott
authors.forename: Jonathan
authors.initials: J
authors.lastname: Laye
authors.forename: Jérémie
authors.initials: J
authors.lastname: Nsengimana
authors.forename: John
authors.initials: J
authors.lastname: Davies
authors.forename: Christy
authors.initials: C
authors.lastname: Walker
authors.forename: Caroline
authors.initials: C
authors.lastname: Conway
authors.forename: Angana
authors.initials: A
authors.lastname: Mitra
authors.forename: Mark
authors.initials: M
authors.lastname: Harland
authors.forename: Martin G
authors.initials: MG
authors.lastname: Cook
authors.forename: Andy
authors.initials: A
authors.lastname: Boon
authors.forename: Sarah
authors.initials: S
authors.lastname: Storr
authors.forename: Sabreena
authors.initials: S
authors.lastname: Safuan
authors.forename: Stewart G
authors.initials: SG
authors.lastname: Martin
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
authors.forename: Håkan
authors.initials: H
authors.lastname: Olsson
authors.forename: Christian
authors.initials: C
authors.lastname: Ingvar
authors.forename: Martin
authors.initials: M
authors.lastname: Lauss
authors.forename: Tim
authors.initials: T
authors.lastname: Bishop
authors.forename: Göran
authors.initials: G
authors.lastname: Jönsson
authors.forename: Julia
authors.initials: J
authors.lastname: Newton-Bishop
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002452:Cell Count; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D015999:Multivariate Analysis; D015398:Signal Transduction / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*; D014456:Ulcer / Q000235:genetics / Q000473:pathology*; D055815:Young Adult
keywords: clinicopathological; gene expression; immunohistochemistry; melanoma; primary; ulceration