Distinction of desmoplastic melanoma from non-desmoplastic melanoma by gene expression profiling.
Desmoplastic melanoma (DM) is a variant of melanoma characterized by the presence of amelanotic fusiform melanocytes dispersed in a prominent collagenous stroma. DM behaves differently from conventional non-desmoplastic melanoma (NDM). It has a higher tendency for local recurrence and is less likely to metastasize to regional lymph nodes. In this study, we explored the possibility of distinguishing DM from NDM by gene expression profiling. RNA samples from ten primary cutaneous melanomas of similar depth of invasion were analyzed using the Affymetrix U133A oligonucleotide platform. Four tumors were DM, five were ND, and one tumor showed combined features of desmoplastic and conventional. Hierarchical cluster analysis clearly separated DM from NDM. The expression of a number of melanocyte differentiation genes was decreased in DM compared with NDM, which corresponded to immunohistochemical results. Various genes were upregulated in DM, including neurotrophic factors and genes involved in extracellular matrix production. A novel finding was the high expression of clusterin in DM, which was confirmed by immunohistochemical studies. Our results from gene expression profiling validate the distinction of DM from NDM. They also provide the opportunity to learn more about the biology of DM which had previously not yet been associated with this variant of melanoma.
Busam
Klaus J
KJ
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. busamk@mskcc.org
Zhao
Hui
H
Coit
Daniel G
DG
Kucukgol
Derya
D
Jungbluth
Achim A
AA
Nobrega
Jennifer
J
Viale
Agnes
A
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D051152:Clusterin; D003937:Diagnosis, Differential; D020869:Gene Expression Profiling / Q000592:standards; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000592:standards; D015203:Reproducibility of Results; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*
D014408:Biomarkers, Tumor; C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones