Differential gene expression profiling of primary cutaneous melanoma and sentinel lymph node metastases.
Koh, SS; Wei, JP; Li, X; Huang, RR; Doan, NB; Scolyer, RA; Cochran, AJ; Binder, SW
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
25
828-37
2012
Show Abstract
Limited understanding of molecular mechanisms of metastasis in melanoma contributes to the absence of effective treatments. Increased knowledge of alterations in genes that underpin critical molecular events that lead to metastasis is essential. We have investigated the gene expression profiles of primary melanomas and melanoma metastases in sentinel lymph nodes. A total of 19 samples (10 primary melanomas and 9 sentinel lymph node metastases) were evaluated. Melanoma cells were dissected from tissue blocks. Total mRNA was isolated, amplified, and labeled using an Ambion Recover All Total Nucleic Acid Isolation kit, Nu-GEN WT-Ovation formalin-fixed, paraffin-embedded RNA Amplification System, and FL-Ovation cDNA Biotin Module V2, respectively. Samples were hybridized to the Affymetrix Gene Chip Human U133 Plus 2.0 Array. Data were analyzed using Partek Genomics Suite Version 6.4. Genes selected showed ≥2-fold difference in expression and Pless than 5.00E-2. Validation studies used standard immunohistochemical assays. Hierarchical clustering disclosed two distinct groups: 10 primary melanomas and 9 sentinel lymph node metastases. Gene expression analysis identified 576 genes that showed significant differential expression. Most differences reflected decreased gene expression in metastases relative to primaries. Reduced gene expression in primaries was less frequent and less dramatic. Genes significantly increased or decreased in sentinel lymph node metastases were active in cell adhesion/structural integrity, tumor suppression, cell cycle regulation, and apoptosis. Validation studies indicate that MAGEC1 (melanoma antigen family C1) and FCRL1 (Fc receptor-like 1) are involved in melanoma progression. There are striking differential gene expression patterns between primary and nodally metastatic melanomas. Similar findings were seen with autologous paired primary melanomas and sentinel lymph node metastases, supporting involvement of these gene alterations in evolution of metastases. With further study, it may be possible to determine the exact sequence of molecular events that underlie melanoma metastases. | 22411186
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MRP-8 and MRP-14, two abundant Ca(2+)-binding proteins of neutrophils and monocytes.
Hessian, P A, et al.
J. Leukoc. Biol., 53: 197-204 (1993)
1993
Show Abstract
Two calcium-binding proteins, named migration inhibitory factor-related proteins-8 (MRP-8) and MRP-14, are primarily expressed by circulating human neutrophils and monocytes. Evidence accumulating from the investigations of several independent groups is now leading to an improved understanding of the biology of these proteins. Both MRP-8 and MRP-14 display features characteristic of members of the S100 family of calcium-binding proteins. Some of these features predict functions for MRP-8 and MRP-14 but to date an exact and well-defined function remains elusive. Here we review the available information and highlight evidence that suggests the function of MRP-8 and MRP-14 may be associated with both monocyte and neutrophil activation and the accumulation of these cells in inflammatory sites. | 8445331
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