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. 2015 Jan;28(1):94-104.
doi: 10.1111/pcmr.12315. Epub 2014 Oct 1.

The clinicopathological and gene expression patterns associated with ulceration of primary melanoma

Rosalyn Jewell  1 , 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
Affiliations

The clinicopathological and gene expression patterns associated with ulceration of primary melanoma

Rosalyn Jewell et al. Pigment Cell Melanoma Res. 2015 Jan.

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: clinicopathological; gene expression; immunohistochemistry; melanoma; primary; ulceration.

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Figures

Figure 1
Figure 1. Flow diagram illustrating the sample sets used for analyses described
Ulceration status data relating to primary melanoma was available for a total of 1804 patients recruited to the Cohort and SNB studies. Gene expression data were available for 348 individual primary tumors from this patient group. This represents the gene expression test set. The first validation dataset (Leeds replication) consisted of an independent set of 124 primary tumors selected from within the Cohort Study. The second validation data set (Lund replication) consisted of 163 primary melanomas. One hundred and ninety-five tumors from the SNB study were used for IHC staining, 130 of these tumors were also cored for gene expression studies in the test set.
See this image and copyright information in PMC

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