title: Investigation of Werner protein as an early DNA damage response in actinic keratosis, Bowen disease and squamous cell carcinoma.
abstract: BACKGROUND
  Werner protein (WRN) has DNA helicase activity and participates in recombination, replication and repair of DNA. Loss-of-function mutations in WRN gives rise to genetic instability and diseases such as premature ageing and cancer. Upregulation of WRN promotes proliferation and survival of cancer cells.
  
  
  OBJECTIVE
  To evaluate the expression pattern of WRN in closely related skin cancers and their correlation with age, sex and UV exposure.
  
  
  METHODS
  Immunohistochemistry was used to investigate expression of WRN in formalin-fixed, paraffin wax-embedded tissue specimens of 9 squamous cell carcinoma (SCC), 15 actinic keratosis (AK), 11 Bowen disease (BD) and 11 normal-appearing peripheral tissue samples, obtained from patients during surgical resections.
  
  
  RESULTS
  WRN expression was significantly increased in BD, AK and SCC compared with normal controls, with the mean WRN staining score being highest in BD, followed by AK and SCC. However, age, sex and sun exposure were not associated with WRN expression.
  
  
  CONCLUSIONS
  To our knowledge, this is the first report to date investigating the expression of WRN in skin cancers. The overtly high expression of WRN in premalignant lesions and in in situ cancer, with relatively low WRN expression in SCC, may indicate that WRN contributes as a checkpoint for early DNA damage response in skin tumorigenesis.
authors.affiliation: Department of Pathology, Ulsan University Hospital, Ulsan, Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Cha
authors.affiliation: Department of Dermatology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: D B
authors.initials: DB
authors.lastname: Lee
authors.affiliation: Department of Dermatology, Ulsan University Hospital, Ulsan, Korea.
authors.forename: H N
authors.initials: HN
authors.lastname: Jung
authors.affiliation: Department of Dermatology, Ulsan University Hospital, Ulsan, Korea.
authors.forename: Y S
authors.initials: YS
authors.lastname: Choi
authors.affiliation: Department of Dermatology, Ulsan University Hospital, Ulsan, Korea.
authors.forename: H S
authors.initials: HS
authors.lastname: Suh
mesh_terms: D000328:Adult; D000368:Aged; D001913:Bowen's Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D004249:DNA Damage; D005090:Exodeoxyribonucleases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D055623:Keratosis, Actinic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D053484:RecQ Helicases / Q000378:metabolism*; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000071657:Werner Syndrome Helicase
chemical_list: D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase