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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.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.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.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. [ABSTRACT FROM AUTHOR]

Assessment of adnexal masses focuses on the accurate discrimination between benign and malignant lesions. In our tertiary referral center, we evaluated the discriminative power of expert sonography, serum CA-125 measurement, risk malignancy index (RMI) by Jacobs, and 2 preoperative triage strategies (combination of CA-125 measurement and RMI assessment with expert sonography).From 2002 to 2008, a total of 1362 surgical explorations with indication of an adnexal mass from our department were included in this study. Preoperative workup in all patients comprised a gynecologic examination, expert sonography, and serum CA-125 measurement. We calculated sensitivity, specificity, positive and negative predictive value (PPV and NPV), and Cohen κ (prevalence-adjusted measurement) to evaluate the discriminative power of each diagnostic test.Discriminative power of the evaluated tests differed depending on patients' menopausal state. In the premenopause, expert sonography reached the highest discriminative power with a κ value of 0.53, a PPV of 0.45, and an NPV of 0.99. In the postmemopause, the combinations of expert sonography with CA-125 serum measurement or RMI assessment achieved the highest discriminative power: The combination of CA-125 and expert sonography reached a PPV of 0.89 and an NPV of 0.97; κ yielded 0.84. The RMI combined with expert sonography as a triage strategy showed comparable results with a PPV of 0.89, an NPV of 0.96, and a κ value of 0.82.Preoperative assessment of an adnexal mass may be guided by the patient's menopausal state. In premenopausal patients, expert sonography is helpful for preoperative differentiation between benign and malignant lesions; in postmenopausal patients, the use of triage strategies of either CA-125 serum measurement or RMI combined with expert sonography can be recommended. [ABSTRACT FROM AUTHOR]