title: P16 is overexpressed in cutaneous carcinomas located on sun-exposed areas.
abstract: BACKGROUND
  Recently, an increased expression of P16, a cell cycle regulatory tumor suppressor protein, has been demonstrated in cervical squamous neoplasms as a marker of malignancy. In contrast, studies performed in skin carcinomas led to contradictory results.
  
  
  OBJECTIVE
  Our first aim was to evaluate P16 expression in different types of non-melanoma skin cancers compared with normal skin and benign tumors. The second aim was to evaluate the relationship between P16 expression and the location of skin tumors (i.e. exposed versus non exposed sites). Finally, we also studied Ki67 expression in skin carcinomas and control biopsies.
  
  
  METHODS
  Skin biopsy specimens with typical histologic features of squamous cell carcinoma (SCC; n = 30), Bowen's disease (BD; n = 17), basal cell carcinoma (BCC; n = 10), seborrheic keratosis (SK; n = 10) and normal human skin (NHS; n = 9) were obtained from 76 patients seen at our institution between 2001 and 2003. In all cases, P16 and Ki67 expression were evaluated by immunohistochemistry and image analysis.
  
  
  RESULTS
  P16 overexpression was observed in 58% of cutaneous carcinomas (SCC: 60%; BD: 58%; BCC: 50%) versus 0% of SK or NHS (0%) (p = 0.006). Ki67 expression in over 5% of tumour cells was observed in 69% of cutaneous carcinomas (SCC: 54%; BD: 76%; BCC: 80%) versus 16% in the group including SK (30%) and NHS (0%) (p = 0.04). Overexpression of P16 was associated with a high rate of Ki67 positive tumour cells in 23/57 malignant skin tumors (40%). Both P16 was associated and Ki-67 were negative in 7/57 cases (12%). Sixty-eight percent of tumors located on sun-exposed areas versus 23% of those located on non sun-exposed areas overexpressed P16 (p = 0.02).
  
  
  CONCLUSIONS
  Our study demonstrated that the expression of P16 and Ki67 is associated with skin carcinomas. No difference was observed according to histological types of carcinomas, suggesting that P16 and Ki67 expression did not correlate with the degree of proliferation and malignancy. Within cutaneous carcinoma specimens, P16 overexpression was significantly associated with the location on sun-exposed areas, suggesting a possible induction of P16 overexpression by UV radiation.
authors.affiliation: CHU Reims, Hôpital Robert Debré, Service de Dermatologie, Avenue du Général Koenig, Reims F-51092, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Conscience
authors.forename: Nicolas
authors.initials: N
authors.lastname: Jovenin
authors.forename: Christelle
authors.initials: C
authors.lastname: Coissard
authors.forename: Marianne
authors.initials: M
authors.lastname: Lorenzato
authors.forename: Anne
authors.initials: A
authors.lastname: Durlach
authors.forename: Florent
authors.initials: F
authors.lastname: Grange
authors.forename: Philippe
authors.initials: P
authors.lastname: Birembaut
authors.forename: Christine
authors.initials: C
authors.lastname: Clavel
authors.forename: Philippe
authors.initials: P
authors.lastname: Bernard
mesh_terms: D000328:Adult; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D014466:Ultraviolet Rays
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen