title: Prognosis of patients with BRCA1-associated ovarian carcinomas depends on TP53 accumulation status in tumor cells.
abstract: OBJECTIVE
  TP53 mutation is the most frequent molecular event in BRCA1-associated ovarian carcinomas. TP53 status may be a confounding factor in the evaluation of clinical importance of other proteins. We aimed to evaluate the clinical significance of BRCA1 mutations with respect to the TP53 accumulation status in 159 high-grade ovarian carcinomas.
  
  
  METHODS
  Statistical analyses were done with the Kaplan-Meier method, log-rank test, the Cox's and logistic regression models for all patients, and in subgroups with and without TP53 accumulation (TP53+ and TP53-, respectively).
  
  
  RESULTS
  Forty of 159 ovarian carcinomas (25.2%) were diagnosed in patients with BRCA1 germline mutations; 102 tumors (64.2%) were TP53+ and 57 (37.8%) were TP53-. Among patients with TP53+ carcinomas, BRCA1 carriers had increased odds of recurrence compared with sporadic cases (HR 2.25, P=0.003; median disease-free survival time 7.7 vs. 18.4months, respectively). In the smaller TP53- subgroup, BRCA1 mutation reduced the risk of death by 46% (HR 0.54, P=0.099, median overall survival time 42.7 vs. 28.1months), but beyond the border of significance. When the TP53 status was not taken into account, BRCA1 mutations did not show any significance, however, there was a trend toward increased odds of complete remission for women with BRCA1 mutations compared to non-carriers (OR 2.47, P=0.064). Taxane-platinum therapy showed advantage over the platinum-cyclophosphamide one in the entire group of patients and in the TP53+ subgroup.
  
  
  CONCLUSIONS
  Our results suggest that the TP53 accumulation status determines the prognosis of BRCA1 mutation carriers with high-grade ovarian carcinomas.
authors.affiliation: Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Iwona K
authors.initials: IK
authors.lastname: Rzepecka
authors.affiliation: Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Lukasz M
authors.initials: LM
authors.lastname: Szafron
authors.affiliation: Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Stys
authors.affiliation: Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Felisiak-Golabek
authors.affiliation: Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Podgorska
authors.affiliation: Department of Obstetrics and Gynecology, Brodnowski Hospital and II-nd Faculty of Medicine, Medical University, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Timorek
authors.affiliation: Department of Gynecologic Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Sobiczewski
authors.affiliation: Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pienkowska-Grela
authors.affiliation: Department of Histopathology, Imperial College London, UK.
authors.forename: Mona
authors.initials: M
authors.lastname: El-Bahrawy
authors.affiliation: Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland. Electronic address: jkupry@coi.waw.pl.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Kupryjanczyk
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics*; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53
keywords: BRCA1; Ovarian cancer; Prognosis; TP53 accumulation