title: Ki-67 and p53 expression of the fallopian tube mucosa in breast cancer patients with hereditary risk.
abstract: OBJECTIVE
  The fallopian tube has been implicated as a site of origin of sporadic and BRCA1-related ovarian cancer. To investigate if Ki-67 or p53 is altered in BRCA1 mutation carriers, we have studied the expression of these markers in morphologically normal mucosa in the fallopian tube and fimbriae.
  
  
  METHODS
  Prophylactic adnexectomy specimens from 24 patients (eight BRCA1 mutation carriers, eight non-mutation carriers, and eight with unknown BRCA1 status), were scored by automated image analysis for the amount of Ki-67 and wild-type p53 expression. All patients had a history of breast cancer and a family history of breast or ovarian cancer.
  
  
  RESULTS
  In the fimbriae, a median of 0.42 % Ki-67 and 0.04 % p53-positive epithelial cells was present, compared to a median of 0.36 % for Ki-67 and 0.05 % for p53 in the fallopian tube. Ki-67 expression decreased significantly with age (r = -0.45, p = 0.028). In contrast, p53 expression was not age-dependent for the whole group of patients (r = 0.25, p = 0.25). Subgroup analysis revealed a difference for p53 expression of the BRCA1 mutation carriers with respect to age (median 0.039 vs. 0.082 % for age less or greater than 50.5 years). Consequently, the p53/Ki-67 ratio showed an age-dependent increase, which was accelerated in the BRCA1-positive patients.
  
  
  CONCLUSIONS
  Ki-67 and p53 expression varies in morphologically normal tubal epithelial cells depending on age and BRCA1 mutation status. This may reflect an altered and age-dependent DNA repair in BRCA1 mutation carriers and may be related to increased risk of ovarian cancer arising in the fallopian tube.
authors.affiliation: Department of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
authors.forename: Alina
authors.initials: A
authors.lastname: Anton
authors.forename: Sarah
authors.initials: S
authors.lastname: Schott
authors.forename: Gisela
authors.initials: G
authors.lastname: Kaip
authors.forename: Michelle
authors.initials: M
authors.lastname: Rath
authors.forename: Jörg
authors.initials: J
authors.lastname: Heil
authors.forename: Sebastian
authors.initials: S
authors.lastname: Aulmann
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Sinn
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics*; D005185:Fallopian Tube Neoplasms / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics*; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics; D012306:Risk; D012959:Socioeconomic Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53