title: Cell cycle regulation and proliferation in lichen sclerosus.
abstract: BACKGROUND
  Genital lichen sclerosus (LS) is considered a potential precursor lesion of squamous cell carcinoma. We aimed to investigate the expression pattern of cell cycle regulators, tumour suppressor proteins and proliferation markers in genital LS as compared to extragenital LS (ELS) and healthy controls (HC).
  
  
  METHODS
  In order to assess the expression of minichromosome maintenance protein 3 (MCM3), MCM7, Ki-67, cyclin D1, cyclin E, p16, p21, and p53, immunohistochemistry and immunofluorescence were performed on skin specimens obtained from the genital region of LS patients (short-standing LS, n=19; long-standing LS, n=15), patients with ELS (n=10), and HC (n=8).
  
  
  RESULTS
  Median protein expression of MCM3 and Ki-67 was significantly higher in LS when compared to ELS and HC. In patients with long-standing LS, the expression profiles of MCM3 and Ki-67 significantly correlated. Moreover, long-standing LS lesions showed significantly increased expression of p53 when compared to short-standing LS, ELS, and HS. Immunoreactivity of MCM7, p16, p21, cyclin D1 and cyclin E did not significantly differ between the groups.
  
  
  CONCLUSIONS
  Tumour suppressor proteins such as p53 are significantly overexpressed in genital LS when compared to extragenital disease and healthy skin. The significant p53 overexpression, particularly in long-standing genital lesions, may reflect the increased risk of malignant transformation and/or oxidative stress associated with LS. Moreover, we have demonstrated that proliferation markers such as Ki-67 and MCM3 are significantly up-regulated in genital LS as compared to controls. With regard to cell cycle regulation and proliferation rates, ELS significantly differs from its genital counterpart.
authors.affiliation: Department of Dermatology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Gambichler
authors.forename: Sara
authors.initials: S
authors.lastname: Kammann
authors.forename: Christian
authors.initials: C
authors.lastname: Tigges
authors.forename: Stephan
authors.initials: S
authors.lastname: Kobus
authors.forename: Marina
authors.initials: M
authors.lastname: Skrygan
authors.forename: Juris J
authors.initials: JJ
authors.lastname: Meier
authors.forename: Christina U
authors.initials: CU
authors.lastname: Köhler
authors.forename: Nina
authors.initials: N
authors.lastname: Scola
authors.forename: Markus
authors.initials: M
authors.lastname: Stücker
authors.forename: Falk G
authors.initials: FG
authors.lastname: Bechara
authors.forename: Peter
authors.initials: P
authors.lastname: Altmeyer
authors.forename: Alexander
authors.initials: A
authors.lastname: Kreuter
mesh_terms: D000368:Aged; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D018459:Lichen Sclerosus et Atrophicus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D064126:Minichromosome Maintenance Complex Component 3; D009687:Nuclear Proteins / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; C066470:MCM3 protein, human; D009687:Nuclear Proteins; D064126:Minichromosome Maintenance Complex Component 3