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Cancers 2018, 10(11), 433;

Cell Origins of High-Grade Serous Ovarian Cancer

Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Indiana University Melvin & Bren Simon Cancer Center, Indianapolis, IN 46202, USA
Department of Pathology and Genomic Medicine, Houston Methodist and Weill Cornell Medical College, Houston, TX 77030, USA
Department of Obstetrics and Gynecology, School of Medicine, Keimyung University, Daegu 41931, Korea
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Author to whom correspondence should be addressed.
Received: 22 October 2018 / Revised: 3 November 2018 / Accepted: 7 November 2018 / Published: 12 November 2018
(This article belongs to the Special Issue The Tumor Microenvironment of High Grade Serous Ovarian Cancer)
PDF [564 KB, uploaded 12 November 2018]


High-grade serous ovarian cancer, also known as high-grade serous carcinoma (HGSC), is the most common and deadliest type of ovarian cancer. HGSC appears to arise from the ovary, fallopian tube, or peritoneum. As most HGSC cases present with widespread peritoneal metastases, it is often not clear where HGSC truly originates. Traditionally, the ovarian surface epithelium (OSE) was long believed to be the origin of HGSC. Since the late 1990s, the fallopian tube epithelium has emerged as a potential primary origin of HGSC. Particularly, serous tubal intraepithelial carcinoma (STIC), a noninvasive tumor lesion formed preferentially in the distal fallopian tube epithelium, was proposed as a precursor for HGSC. It was hypothesized that STIC lesions would progress, over time, to malignant and metastatic HGSC, arising from the fallopian tube or after implanting on the ovary or peritoneum. Many clinical studies and several mouse models support the fallopian tube STIC origin of HGSC. Current evidence indicates that STIC may serve as a precursor for HGSC in high-risk women carrying germline BRCA1 or 2 mutations. Yet not all STIC lesions appear to progress to clinical HGSCs, nor would all HGSCs arise from STIC lesions, even in high-risk women. Moreover, the clinical importance of STIC remains less clear in women in the general population, in which 85–90% of all HGSCs arise. Recently, increasing attention has been brought to the possibility that many potential precursor or premalignant lesions, though composed of microscopically—and genetically—cancerous cells, do not advance to malignant tumors or lethal malignancies. Hence, rigorous causal evidence would be crucial to establish that STIC is a bona fide premalignant lesion for metastatic HGSC. While not all STICs may transform into malignant tumors, these lesions are clearly associated with increased risk for HGSC. Identification of the molecular characteristics of STICs that predict their malignant potential and clinical behavior would bolster the clinical importance of STIC. Also, as STIC lesions alone cannot account for all HGSCs, other potential cellular origins of HGSC need to be investigated. The fallopian tube stroma in mice, for instance, has been shown to be capable of giving rise to metastatic HGSC, which faithfully recapitulates the clinical behavior and molecular aspect of human HGSC. Elucidating the precise cell(s) of origin of HGSC will be critical for improving the early detection and prevention of ovarian cancer, ultimately reducing ovarian cancer mortality. View Full-Text
Keywords: ovarian cancer; epithelial ovarian cancer; high-grade serous ovarian cancer (HGSOC); high-grade serous carcinoma (HGSC); ovarian cancer origin; fallopian tube; ovarian surface epithelium (OSE); serous tubal intraepithelial carcinoma (STIC) ovarian cancer; epithelial ovarian cancer; high-grade serous ovarian cancer (HGSOC); high-grade serous carcinoma (HGSC); ovarian cancer origin; fallopian tube; ovarian surface epithelium (OSE); serous tubal intraepithelial carcinoma (STIC)

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Kim, J.; Park, E.Y.; Kim, O.; Schilder, J.M.; Coffey, D.M.; Cho, C.-H.; Bast, R.C., Jr. Cell Origins of High-Grade Serous Ovarian Cancer. Cancers 2018, 10, 433.

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