Microvesicle proteomics of 187 utero-tubal lavage samples for early diagnosis of HGOC.• Machine learning-based classification of a 9-protein signature with high predictive power.• Signature has 70% sensitivity and 76.2% specificity, predicting stage I lesions.

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In recent years, the notion that ovarian carcinoma results from ovulation-induced inflammation of the fallopian tube epithelial cells (FTECs) has gained evidence. However, the mechanistic pathway for this process has not been revealed yet. In the current study, we propose the mutator protein activation-induced cytidine deaminase (AID) as a link between ovulation-induced inflammation in FTECs and genotoxic damage leading to ovarian carcinogenesis. We show that AID, previously shown to be functional only in B lymphocytes, is expressed in FTECs under physiological conditions, and is induced in vitro upon ovulatory-like stimulation and in vivo in carcinoma-associated FTECs. We also report that AID activity results in epigenetic, genetic and genomic damage in FTECs. Overall, our data provides new insights into the etiology of ovarian carcinogenesis and may set the ground for innovative approaches aimed at prevention and early detection.

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Delayed diagnosis of ovarian cancer, as well as high recurrence rates and lack of personalized therapy options, are among the causes for poor survival figures. Much effort is made towards developing new therapeutic possibilities, however predictive biomarkers are still unavailable. CCNE1 amplification, occurring in ∼20% of the high grade serous ovarian tumors, was previously proposed as a marker for platinum resistance and poor prognosis as well as for CDK2 inhibition. The current study aimed to examine the role of CCNE1 positive-immunostain as a predictor of first-line taxane-platinum chemoresistance. We evaluated matched pre- vs. post-neoadjuvant chemotherapy tumor samples and correlated the degree of pathological response to treatment with CCNE1 expression levels. Our results indicate that CCNE1 immunohistochemistry does not predict taxane-platinum chemoresistance in ovarian cancer patients. Further research is required in order to enable personalized adjuvant treatment, in cases where poor pathological response is achieved after the neoadjuvant phase.