RT Journal Article
SR Electronic
T1 Loss of BRCA1 Protein Expression as Indicator of the BRCAness Phenotype Is Associated With Favorable Overall Survival After Complete Resection of Sporadic Ovarian Cancer
JF International Journal of Gynecologic Cancer
JO Int J Gynecol Cancer
FD BMJ Publishing Group Ltd
SP 1399
OP 1406
DO 10.1097/IGC.0b013e318227c990
VO 21
IS 8
A1 Marc P. Radosa
A1 Norman Häfner
A1 Oumar Camara
A1 Herbert Diebolder
A1 Anke Mothes
A1 Harald Winzer
A1 Lars Jansen
A1 Matthias Dürst
A1 Ingo B. Runnebaum
YR 2011
UL http://ijgc.bmj.com/content/21/8/1399.abstract
AB 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.Conclusion: 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.