title: Expression of p53, p21 and cyclin D1 in penile cancer: p53 predicts poor prognosis.
abstract: OBJECTIVE
  To evaluate the role of p53, p21 and cyclin D1 expression in patients with penile cancer (PC).
  
  
  METHODS
  Paraffin-embedded tissues from PC specimens from six pathology departments were subjected to a central histopathological review performed by one pathologist. The tissue microarray technique was used for immunostaining which was evaluated by two independent pathologists and correlated with cancer-specific survival (CSS). κ-statistics were used to assess interobserver variability. Uni- and multivariable Cox proportional hazards analysis was applied to assess the independent effects of several prognostic factors on CSS over a median of 32 months (IQR 6-66 months).
  
  
  RESULTS
  Specimens and clinical data from 110 men treated surgically for primary PC were collected. p53 staining was positive in 30 and negative in 62 specimens. κ-statistics showed substantial interobserver reproducibility of p53 staining evaluation (κ=0.73; p<0.001). The 5-year CSS rate for the entire study cohort was 74%. Five-year CSS was 84% in p53-negative and 51% in p53-positive PC patients (p=0.003). Multivariable analysis showed p53 (HR=3.20; p=0.041) and pT-stage (HR=4.29; p<0.001) as independent significant prognostic factors for CSS. Cyclin D1 and p21 expression were not correlated with survival. However, incorporating p21 into a multivariable Cox model did contribute to improved model quality for predicting CSS.
  
  
  CONCLUSIONS
  In patients with PC, the expression of p53 in the primary tumour specimen can be reproducibly assessed and is negatively associated with cancer specific survival.
authors.affiliation: Institute of Pathology, HELIOS Clinic Bad Saarow, Germany. sven.gunia@helios-kliniken.de
authors.forename: Sven
authors.initials: S
authors.lastname: Gunia
authors.forename: Christoph
authors.initials: C
authors.lastname: Kakies
authors.forename: Andreas
authors.initials: A
authors.lastname: Erbersdobler
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Hakenberg
authors.forename: Stefan
authors.initials: S
authors.lastname: Koch
authors.forename: Matthias
authors.initials: M
authors.lastname: May
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D016009:Chi-Square Distribution; D019938:Cyclin D1 / Q000032:analysis*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis*; D018572:Disease-Free Survival; D005858:Germany; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D015999:Multivariate Analysis; D016612:Paraffin Embedding; D010412:Penile Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1