The Origin of Ovarian Cancer Species and Precancerous Landscape

Abstract

Unlike other human cancers, in which all primary tumors arise de novo, ovarian epithelial cancers are primarily imported from either endometrial or fallopian tube epithelium. The prevailing paradigm in the genesis of high-grade serous carcinoma (HGSC), the most common ovarian cancer, posits to its development in fallopian tubes through stepwise tumor progression. Recent progress has been made not only in gathering terabytes of omics data but also in detailing the histologicemolecular correlations required for looking into, and making sense of, the tissue origin of HGSC. This emerging paradigm is changing many facets of ovarian cancer research and routine gynecology practice. The precancerous landscape in fallopian tubes contains multiple concurrent precursor lesions, including serous tubal intraepithelial carcinoma (STIC), with genetic heterogeneity providing a platform for HGSC evolution. Mathematical models imply that a prolonged time (decades) elapses from the development of a TP53 mutation, the earliest known molecular alteration, to an STIC, followed by a shorter span (6 years) for progression to an HGSC. Genetic predisposition accelerates the trajectory. This timeline may allow for the early diagnosis of HGSC and STIC, followed by intent-to-cure surgery. This review discusses the recent advances in this tubal paradigm and its biological and clinical implications, alongside the promise and challenge of studying STIC and other precancerous lesions of HGSC.

Progesterone Receptor Membrane Component (PGRMC)1 and PGRMC2 and Their Roles in Ovarian and Endometrial Cancer

“…Although the ovary and uterus have very different functions, the cancers that develop within these organs have several common characteristics. In fact, some findings suggest that ovarian epithelial cancers are derived from either endometrial or fallopian tube epithelium [ 1 ] and are sometimes collectively referred to as pelvic floor cancers [ 2 ]. Moreover, both cancers are hormonally regulated [ 3 , 4 , 5 ] and they express various progesterone (P4) receptors [ 1 , 3 , 4 ].…”

“…In fact, some findings suggest that ovarian epithelial cancers are derived from either endometrial or fallopian tube epithelium [ 1 ] and are sometimes collectively referred to as pelvic floor cancers [ 2 ]. Moreover, both cancers are hormonally regulated [ 3 , 4 , 5 ] and they express various progesterone (P4) receptors [ 1 , 3 , 4 ]. One characteristic that is not often appreciated is that they express members of the P4 receptor membrane component (PGRMC) family, most notably PGRMC1 and PGRMC2 (for review see [ 1 ]).…”

Shaping Immune Responses in the Tumor Microenvironment of Ovarian Cancer

“…Due to nearly 75% of OvCa patients are diagnosed at a late stage with widespread intra-abdominal metastasis, cytoreductive surgery and primary chemotherapy with platinum agent and taxane have not been very effective ( 97 ). The majority (over 70%) of patients will relapse, with 5-year survival rates of approximately 30% and the proportion of patients who remain cancer-free at 10 years is less than 15% ( 98 ). Based on the detailed evidence with existing studies, certain disease mechanisms can be chosen as treatment targets.…”

Development of Small Molecule Inhibitors Targeting PBX1 Transcription Signaling as a Novel Cancer Therapeutic Strategy

“…Tumor (nuclear) grade has been established as an important factor affecting clinical outcome in ovarian serous carcinomas (25,26). Based on the Kaplan-Meier (K-M) Plotter portal (27), we analyzed PBX1 expression and clinical outcome in women with ovarian serous cancers.…”