Screening and Prevention for High-Grade Serous Carcinoma of the Ovary Based on Carcinogenesis—Fallopian Tube- and Ovarian-Derived Tumors and Incessant Retrograde Bleeding

Abstract

High-grade serous carcinoma (HGSC) is the most common and lethal subtype of ovarian carcinoma. Many HGSCs are now believed to originate in the fallopian tube epithelium; ovarian surface epithelium is another possible origin. Thus, current screening methods, i.e., ultrasonography and serum CA-125 measurements, have a limitation in their early detection. Recently, circulating biomarkers, such as tumor DNA, autoantibody, and microRNA, have been investigated to detect HGSCs. As cancer cells in the fallopian tube flow into the endometrial cavity, the detection of exfoliated cells, tumor DNA, and proteome from samples obtained from the endometrial cavity or the cervix may be useful. The risk of ovarian serous carcinoma is affected by the use of oral contraceptive and menopausal hormone therapy (MHT). MHT regimens causing endometrial bleeding increase serous carcinoma risk, hence, incessant retrograde bleeding from the endometrial cavity into the Douglas pouch appears to play an important role in high-grade serous carcinogenesis. In this review, we provide an overview of current and novel screening methods and prevention approaches for ovarian and fallopian tube HGSC.

Mechanisms of High-Grade Serous Carcinogenesis in the Fallopian Tube and Ovary: Current Hypotheses, Etiologic Factors, and Molecular Alterations

“…Incessant retrograde bleeding is an expansion of the concept of incessant menstruation and may explain more accurately the etiology of HGSCs in both premenopausal and postmenopausal women [ 19 ]. Some types of MHT, also called hormone replacement therapy, increase ovarian cancer risk.…”

“…Both regimens cause endometrial bleeding. In contrast, serous ovarian cancer risk is not altered by the use of continuous estrogen and progestin, which results in endometrial atrophy with bleeding cessation [ 19 , 21 ]. Thus, MHT regimens that cause endometrial bleeding are associated with an increased risk of serous ovarian carcinoma.…”

Understanding and addressing barriers to successful adenovirus-based virotherapy for ovarian cancer

“…Together with the fact that the use of these screening methods did not show a significant mortality reduction, there is thus no available screening routine for the general population at the present time. Novel approaches based on the detection of specific circulating tumor DNA and miRNAs are under investigation, but those methods are not yet capable of detecting asymptomatic disease [5][6][7]. Even though chemotherapy is successful at the time of presentation, around 70% of patients have recurrence in the first 3 year, and 15% relapse with chemoresistant disease, that is not curable [8].…”

“…Metastatic tumors also seed in other organs of the peritoneum, but only invade the superficial layers of tissue [17,18]. In fact, the exfoliation capability from small masses difficults HGSOC screening [7]. Two key features of disease progression are the characteristic anoikis resistance of EOC cells and their ability to attach to the mesothelial cells covering the peritoneal organs [17,19], a process where matrix metalloproteinases (MMP-2) and integrins (α5β1 and αVβ3) are largely involved [20][21][22].…”

Frontline Management of Epithelial Ovarian Cancer—Combining Clinical Expertise with Community Practice Collaboration and Cutting-Edge Research

“…Circulating miRNAs in blood and urine are being explored as potential early detection markers. However, the evidence on this approach is currently limited, and no consistent miRNA signatures have emerged [ 44 , 45 , 46 ]. The lack of reproducibility may be attributable, in part, to technical issues, such as different statistical modeling and approaches, the utilization of different miRNA detection platforms, and patient and tumor heterogeneity [ 46 ].…”