title: The N-terminally truncated p53 isoform Δ40p53 influences prognosis in mucinous ovarian cancer.
abstract: OBJECTIVE
  The tumor suppressor p53 generates the N-terminally truncated isoforms Δ40p53 and Δ133p53 that possess the ability to modulate p53 function in vitro. The aim of the present study was to evaluate the clinical relevance of p53 isoforms in the main histological subtypes of ovarian cancer.
  
  
  METHODS
  Δ40p53, Δ133p53, and full-length p53 (FLp53) expression was determined in 45 mucinous, 30 endometrioid, and 91 serous ovarian cancer specimens as well as 42 normal ovarian tissues using reverse transcriptase-quantitative polymerase chain reaction. In a subgroup of mucinous ovarian cancer cases, Δ40p53 expression was examined using Western blot analysis. A functional yeast-based assay and subsequent sequencing were performed to analyze the p53 mutational status.
  
  
  RESULTS
  In endometrioid cancer specimens, Δ133p53 expression was significantly lower than in mucinous and serous cases (P = 0.016) or in normal tissues (P = 0.004). Mucinous cancer samples showed elevated Δ40p53 expression as compared with normal ovarian tissues (P = 0.003). In addition, high Δ40p53 expression constituted an independent prognostic marker for recurrence-free but not for overall survival in patients with mucinous ovarian cancer (hazard ratio, 0.267; 95% confidence interval, 0.094-0.756 [P = 0.013]; hazard ratio, 0.453, 95% confidence interval, 0.193-1.064 [P = 0.069]). Western blot analysis confirmed the presence of p53β and Δ40p53α in a subset of patients with mucinous ovarian cancer. Expression of p53 isoforms was not associated with p53 mutational status or clinicopathologic parameters.
  
  
  CONCLUSIONS
  We show that expression of p53 isoforms differs in histological subtypes, thus supporting the hypothesis that histological subtypes represent distinct disease entities. In addition, we provide first evidence for a favorable role of Δ40p53 in patients with mucinous ovarian cancer.
authors.affiliation: Department of Gynecology and Obstetrics, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Gerda
authors.initials: G
authors.lastname: Hofstetter
authors.forename: Astrid
authors.initials: A
authors.lastname: Berger
authors.forename: Regina
authors.initials: R
authors.lastname: Berger
authors.forename: Arijana
authors.initials: A
authors.lastname: Zorić
authors.forename: Elena I
authors.initials: EI
authors.lastname: Braicu
authors.forename: Daniel
authors.initials: D
authors.lastname: Reimer
authors.forename: Heidi
authors.initials: H
authors.lastname: Fiegl
authors.forename: Christian
authors.initials: C
authors.lastname: Marth
authors.forename: Alain G
authors.initials: AG
authors.lastname: Zeimet
authors.forename: Hanno
authors.initials: H
authors.lastname: Ulmer
authors.forename: Ute
authors.initials: U
authors.lastname: Moll
authors.forename: Robert
authors.initials: R
authors.lastname: Zeillinger
authors.forename: Nicole
authors.initials: N
authors.lastname: Concin
mesh_terms: D017024:Chemotherapy, Adjuvant; D018389:Codon, Nonsense / Q000502:physiology; D018291:Cystadenoma, Mucinous / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D013509:Gynecologic Surgical Procedures; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000628:therapy; D011379:Prognosis; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
chemical_list: D018389:Codon, Nonsense; D020033:Protein Isoforms; D016159:Tumor Suppressor Protein p53