title: No differences in p53 mutation frequencies between BRCA1-associated and sporadic ovarian cancers.
abstract: OBJECTIVE
  Mutation of the BRCA1 gene, which has incomplete penetrance, is involved in ovarian cancer development. Cell cycle check point inactivation via acquired somatic mutations in the check point regulatory genes, particularly p53, may be required for BRCA1-linked ovarian tumorigenesis. In the few studies directly comparing p53 mutations in BRCA1-linked and sporadic ovarian cancers, data have been contradictory. This study aimed to clarify the role of p53 mutation in BRCA1-associated and sporadic ovarian cancer by comparing two, large, matched cohorts from two different populations who developed BRCA1-linked or sporadic ovarian cancers.
  
  
  METHODS
  Forty-eight BRCA1-associated ovarian tumor samples (22 from Australia and 26 from Norway) were collected and matched with 48 sporadic ovarian cancers for tumor stage, grade, histological subtype, and patient age. Expression of p53 protein was measured by immunohistochemistry (IHC).
  
  
  RESULTS
  Consistent with the presence of a mutated p53 protein, the majority of BRCA1-associated (79%) and sporadic (73%) ovarian carcinomas from Australia and Norway overexpressed p53 protein. There was no significant difference between BRCA1-linked ovarian cancers and their sporadic counterparts with regard to p53 protein expression (P = 0.5).
  
  
  CONCLUSIONS
  Our results suggest that p53 inactivation is associated with both BRCA1-associated and sporadic ovarian tumorigenesis, and that BRCA1-linked and sporadic ovarian cancers may develop through a similar carcinogenic pathway.
authors.affiliation: Oncology Research Centre, Prince of Wales Hospital, Randwick, NSW 2031, Australia.
authors.forename: Morteza
authors.initials: M
authors.lastname: Aghmesheh
authors.forename: Jahn M
authors.initials: JM
authors.lastname: Nesland
authors.forename: Janne
authors.initials: J
authors.lastname: Kaern
authors.forename: Anne
authors.initials: A
authors.lastname: Dorum
authors.forename: Lyndal
authors.initials: L
authors.lastname: Edwards
authors.forename: Karen
authors.initials: K
authors.lastname: Byth
authors.forename: Michael
authors.initials: M
authors.lastname: Friedlander
authors.forename: Paul
authors.initials: P
authors.lastname: Jackson
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Tucker
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Russell
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D019398:Genes, BRCA1; D016158:Genes, p53 / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020125:Mutation, Missense; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D016159:Tumor Suppressor Protein p53