Proteomic signature for detection of high-grade ovarian cancer in germline BRCA mutation carriers.

No current screening methods for high-grade ovarian cancer (HGOC) guarantee effective early detection for high-risk women such as germline BRCA mutation carriers. Therefore, the standard-of-care remains risk-reducing salpingo-oophorectomy (RRSO) around age 40. Proximal liquid biopsy is a promising source of biomarkers, but sensitivity has not yet qualified for clinical implementation. We aimed to develop a proteomic assay based on proximal liquid biopsy, as a decision support tool for monitoring high-risk population. Ninety Israeli BRCA1 or BRCA2 mutation carriers were included in the training set (17 HGOC patients and 73 asymptomatic women), (BEDOCA trial; ClinicalTrials.gov Identifier: NCT03150121). The proteome of the microvesicle fraction of the samples was profiled by mass spectrometry and a classifier was developed using logistic regression. An independent cohort of 98 BRCA mutation carriers was used for validation. Safety information was collected for all women who opted for uterine lavage in a clinic setting. We present a 7-protein diagnostic signature, with AUC >0.97 and a negative predictive value (NPV) of 100% for detecting HGOC. The AUC of the biomarker in the independent validation set was >0.94 and the NPV >99%. The sampling procedure was clinically acceptable, with favorable pain scores and safety. We conclude that the acquisition of Müllerian tract proximal liquid biopsies in women at high-risk for HGOC and the application of the BRCA-specific diagnostic assay demonstrates high sensitivity, specificity, technical feasibility and safety. Similar classifier for an average-risk population is warranted.

Disparity in post-treatment maternal circulating magnesium sulfate levels between twin and singleton gestation: Is this the missing link between plurality and adverse outcome?

OBJECTIVE: Magnesium sulfate (MgSO4) administered to women at risk for preterm delivery decreases the risk of cerebral palsy in their children. However, the neuroprotective effect of MgSO4 has not been shown in twin gestations. Thus, the aim of this study was to determine the maternal serum levels of magnesium in twin vs. singleton pregnancies following intravenous treatment of MgSO4. METHODS: Case control study including two groups of pregnant women who received intravenous MgSO4: (1) twin gestations (n=83) and (2) singleton pregnancies (n=83). Maternal serum magnesium levels 6 and 24 h after initiation of treatment were determined in both groups. RESULTS: Maternal serum levels of magnesium were significantly lower among patients with twin gestations compared to those with singleton ones 6 h after initiation of treatment (4.6 vs. 4.8 mg/dL, P=0.003). In addition, the rate of pregnant women who obtained therapeutic levels 6 h after initiation of treatment was significantly lower in twin gestations than in singleton ones (36% vs. 58%, P=0.008). Multiple regression analysis revealed that twin gestations were independently and significantly associated with low maternal serum magnesium levels. CONCLUSIONS: Maternal serum concentrations of magnesium are lower in twin pregnancies than in singleton ones following MgSO4 treatment, which might explain the decreased neuroprotective effect of MgSO4 reported in twin pregnancies.