title: Discrimination of Dysplastic Nevi from Common Melanocytic Nevi by Cellular and Molecular Criteria.
abstract: Dysplastic nevi (DNs), also known as Clark's nevi or atypical moles, are distinguished from common melanocytic nevi by variegation in pigmentation and clinical appearance, as well as differences in tissue patterning. However, cellular and molecular differences between DNs and common melanocytic nevi are not completely understood. Using cDNA microarray, quantitative RT-PCR, and immunohistochemistry, we molecularly characterized DNs and analyzed the difference between DNs and common melanocytic nevi. A total of 111 probesets (91 annotated genes, fold change > 2.0 and false discovery rate < 0.25) were differentially expressed between the two lesions. An unexpected finding in DNs was altered differentiation and activation of epidermal keratinocytes with increased expression of hair follicle-related molecules (keratin 25, trichohyalin, ribonuclease, RNase A family, 7) and inflammation-related molecules (S100A7, S100A8) at both genomic and protein levels. The immune microenvironment of DNs was characterized by an increase of T helper type 1 (IFNγ) and T helper type 2 (IL13) cytokines as well as an upregulation of oncostatin M and CXCL1. DUSP3, which regulates cellular senescence, was identified as one of the disease discriminative genes between DNs and common melanocytic nevi by three independent statistical approaches and its altered expression was confirmed by immunohistochemistry. The molecular and cellular changes in which the epidermal-melanin unit undergoes follicular differentiation as well as upregulation of defined cytokines could drive complex immune, epidermal, and pigmentary alterations.
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mitsui
authors.affiliation: Department of Dermatology and Allergy, Skin Cancer Center, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Kiecker
authors.affiliation: Department of Dermatology, Tel-Hashomer Medical Center, Ramat-Gan, Israel.
authors.forename: Avner
authors.initials: A
authors.lastname: Shemer
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA; Department of Dermatology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Cannizzaro
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Claire Q F
authors.initials: CQF
authors.lastname: Wang
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Gulati
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Hanako
authors.initials: H
authors.lastname: Ohmatsu
authors.affiliation: Texas Dermatology Associates, Baylor University Medical Center, Dallas, Texas, USA.
authors.forename: Kejal R
authors.initials: KR
authors.lastname: Shah
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Gilleaudeau
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Sullivan-Whalen
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Inna
authors.initials: I
authors.lastname: Cueto
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Neil Scott
authors.initials: NS
authors.lastname: McNutt
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA; Center for Clinical and Translational Science, The Rockefeller University, New York, New York, USA.
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA. Electronic address: jgk@rockefeller.edu.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
mesh_terms: D002454:Cell Differentiation; D016922:Cellular Senescence / Q000235:genetics; D016207:Cytokines / Q000276:immunology; D003937:Diagnosis, Differential; D054640:Dual Specificity Phosphatase 3 / Q000235:genetics; D004416:Dysplastic Nevus Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D018859:Hair Follicle / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D015603:Keratinocytes / Q000166:cytology*; D009508:Nevus, Pigmented / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015854:Up-Regulation
chemical_list: D016207:Cytokines; C517025:DUSP3 protein, human; D054640:Dual Specificity Phosphatase 3