title: Coexpression of SOX10/CD271 (p75(NTR)) and β-Galactosidase in Large to Giant Congenital Melanocytic Nevi of Pediatric Patients.
abstract: BACKGROUND
  Congenital melanocytic nevi (CMNs) are melanocytic neoplasms that can transform into melanoma. However, this development is impeded in the majority of cases and mostly affects patients with large or giant CMNs.
  
  
  METHODS
  To elucidate mechanisms that keep CMNs from malignant transformation, CMN tissue biopsies were investigated for p-ERK and senescence markers by immunohistochemistry and for SOX10/CD271 (p75(NTR)) by immunofluorescence. CMN cells were cultivated, and MTT assays were performed for evaluating cell viability. Mutation status for NRAS and BRAF was performed by real-time PCR.
  
  
  RESULTS
  13 CMNs (from patients aged 0.5-11.8 years, mean: 2.7) showed immunoreactivity for SOX10/CD271 (p75(NTR)) in 34.2%. p-ERK was immunoreactive in 80% (4/5); β-galactosidase was significantly stronger expressed in CMNs compared to melanocytic nevi of patients over 70 years (p = 0.0085). The 5 CMN cultures were immunoreactive for SOX10/CD271 (p75(NTR)) in 36.7%. By silencing SOX10 by siRNA in 2 CMN cell cultures, cell viability decreased significantly. NRAS(Q61K) mutation was found in 91.7% (11/12) and BRAF(V600E) in 6.3% of all analyzable CMNs (1/16).
  
  
  CONCLUSIONS
  Oncogene-induced senescence might prevent malignant transformation through activation of the mitogen-activated protein kinase pathway. SOX10 is necessary for the viability of human CMN cell cultures and may be responsible for clinical changes during aging.
authors.affiliation: Department of Dermatology, University Hospital Zurich, Switzerland.
authors.forename: Marjam J
authors.initials: MJ
authors.lastname: Barysch
authors.affiliation: Department of Dermatology, University Hospital Zurich, Switzerland.
authors.forename: Mitchell P
authors.initials: MP
authors.lastname: Levesque
authors.affiliation: Department of Dermatology, University Hospital Zurich, Switzerland.
authors.forename: Phil
authors.initials: P
authors.lastname: Cheng
authors.affiliation: Department of Dermatology, University Hospital Zurich, Switzerland.
authors.forename: Maria B
authors.initials: MB
authors.lastname: Karpova
authors.affiliation: Department of Pathology, University Hospital Zurich, Switzerland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Mihic-Probst
authors.affiliation: Laboratories of Experimental Oncology, Department of Anatomy, Institute of Oncology Research, Bellinzona, Switzerland.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Civenni
authors.affiliation: Institute of Anatomy, University Zurich, Switzerland.
authors.forename: Olga
authors.initials: O
authors.lastname: Shakhova
authors.affiliation: Institute of Anatomy, University Zurich, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: Sommer
authors.affiliation: Pediatric Burn Centre, Plastic and Reconstructive Surgery, Department of Surgery, University Children's Hospital Zurich, Switzerland; Children's Research Center, Zurich, Department of Anatomy, Institute of Oncology Research, Bellinzona, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Biedermann
authors.affiliation: Pediatric Burn Centre, Plastic and Reconstructive Surgery, Department of Surgery, University Children's Hospital Zurich, Switzerland; Children's Research Center, Zurich, Department of Anatomy, Institute of Oncology Research, Bellinzona, Switzerland.
authors.forename: Clemens
authors.initials: C
authors.lastname: Schiestl
authors.affiliation: Department of Dermatology, University Hospital Zurich, Switzerland.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
keywords: BRAF; Congenital melanocytic nevi; Melanoma; NRAS; Neural crest; Nevus; SOX10; Stem cells