title: p16INK4a and p21Waf1/Cip1 expression correlates with clinical outcome in vulvar carcinomas.
abstract: OBJECTIVE
  Aberrant expression of the cell cycle kinase inhibitors p16, p21, and p27 has been associated with poor prognosis in a variety of human malignancies. Little is known, however, about their clinical impact in vulvar carcinoma patients. Thus, we analyzed a larger series of vulvar squamous cell carcinomas and compared the results with clinical outcome.
  
  
  METHODS
  A total of 224 vulvar squamous cell carcinomas were immunohistochemically investigated for expression of p16, p21, and p27 using the biotin-streptavidin-peroxidase method and the OptiMax Plus automated cell staining system.
  
  
  RESULTS
  High p16 (> or =5%) positive nuclear immunostaining was found in 69 (31%) cases, high p21 (any staining) protein levels was detected in 95 (42%) cases, and low p27 (< or =50% positive nuclei) staining was seen in 170 (76%) cases. High expression of p16 was related to lower patient age and low expression of p53. High expression of p16 indicated a better prognosis in the multivariate analysis (RR = 0.5, 95% CI = 0.2-1.0) and less risk of developing lymph node metastasis (OR = 0.3, 95% CI = 0.2-0.7). High level of p21 was significantly associated with shorter survival in patients staged FIGO I and II (RR = 3.4, 95% CI = 1.3-9.3). We found no significant correlation between the expression of p27 and any of the clinicopathological variables.
  
  
  CONCLUSIONS
  Our study indicates a prognostic relevance for p16 and p21 immunoreactivity. Low level of p16 protein and high level of p21 protein were associated with a shorter disease-related survival. We did not find p27 protein expression to be useful as a prognostic indicator in vulvar carcinoma patients.
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, University of Oslo, 0310 Oslo, Norway. synne.nopp@klinmet.uio.no
authors.forename: Synne
authors.initials: S
authors.lastname: Knopp
authors.forename: Tone
authors.initials: T
authors.lastname: Bjørge
authors.forename: Jahn M
authors.initials: JM
authors.lastname: Nesland
authors.forename: Claes
authors.initials: C
authors.lastname: Tropé
authors.forename: Marit
authors.initials: M
authors.lastname: Scheistrøen
authors.forename: Ruth
authors.initials: R
authors.lastname: Holm
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D012189:Retrospective Studies; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis; D014846:Vulvar Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27