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The clinicopathological and gene expression patterns associated with ulceration of primary melanoma |
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| Authors: | Rosalyn Jewell Faye Elliott Jonathan Laye Jérémie Nsengimana John Davies Christy Walker Caroline Conway Angana Mitra Mark Harland Martin G Cook Andy Boon Sarah Storr Sabreena Safuan Stewart G Martin Karin Jirström Håkan Olsson Christian Ingvar Martin Lauss Tim Bishop Göran Jönsson Julia Newton‐Bishop |
| Institution: | 1. Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK;2. Division of Medicine, Royal Surrey County Hospital NHS Foundation Trust, University of Surrey, Guildford, UK;3. Leeds Teaching Hospitals NHS Trust, Leeds, UK;4. Academic Oncology, School of Molecular Medical Sciences, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK;5. Department of Pathology, Lund University, Lund, Sweden;6. Department of Oncology, Lund University, Lund, Sweden;7. Department of Surgery, Lund University, Lund, Sweden |
| 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. |
| Keywords: | melanoma primary ulceration gene expression clinicopathological immunohistochemistry |