title: Loss of BRCA1 protein expression as indicator of the BRCAness phenotype is associated with favorable overall survival after complete resection of sporadic ovarian cancer.
abstract: OBJECTIVE
  Hereditary epithelial ovarian cancers (EOCs) not expressing functional BRCA1 protein are characterized by defects in homologous recombination DNA repair, rendering such tumors more sensitive to DNA damaging agents and synthetic lethality, that is, poly-ADP-ribose-polymerase inhibitor treatment. The aim of this study was to evaluate the use of BRCA1 immunohistochemistry (IHC) for EOC prognosis and identification of features of the BRCAness phenotype.
  
  
  METHODS
  Twenty-seven patients who were treated for advanced EOC by macroscopic complete surgical tumor resection and first-line carboplatin/paclitaxel treatment were included. Time to recurrence and overall survival time after initial surgery were determined, and patients' samples were evaluated for BRCA1 expression by IHC. BRCA1 messenger RNA expression and promoter methylation was analyzed to elucidate regulatory mechanisms involved in BRCA1 protein loss.
  
  
  RESULTS
  BRCA1 IHC-negative patients had a significantly longer overall survival (crude rate, 1537 days) compared to the BRCA1 IHC-positive group (crude rate, 827 days; P = 0.01). The patients in the BRCA1 IHC-negative group were significantly younger (51 years) compared to BRCA1 IHC-positive patients (61 years; P < 0.01). Importantly, both transcriptional and posttranscriptional mechanisms regulate BRCA1 protein expression. Only protein but not messenger RNA level were associated with longer overall survival.
  
  
  CONCLUSIONS
  Epithelial ovarian cancers with negative BRCA1 protein expression were identified in younger patients, showed a significantly better overall survival, prolonged treatment intervals and a tendency for an extended progression free time interval. BRCA1 IHC negativity of sporadic EOC may be predictive of sensitivity to platinum-based chemotherapy and the poly-ADP-ribose-polymerase inhibitor-sensitive BRCAness phenotype.
authors: Department of Gynecology and Obstetrics, Jena University Hospital, Jena, Germany.
authors: Marc P
authors: MP
authors: Radosa
authors: Norman
authors: N
authors: Häfner
authors: Oumar
authors: O
authors: Camara
authors: Herbert
authors: H
authors: Diebolder
authors: Anke
authors: A
authors: Mothes
authors: Harald
authors: H
authors: Winzer
authors: Lars
authors: L
authors: Jansen
authors: Matthias
authors: M
authors: Dürst
authors: Ingo B
authors: IB
authors: Runnebaum
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019313:BRCA1 Protein / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016190:Carboplatin / Q000627:therapeutic use; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D017239:Paclitaxel / Q000627:therapeutic use; D010641:Phenotype; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; D014408:Biomarkers, Tumor; D016190:Carboplatin; D017239:Paclitaxel