<p>The Diagnosis, Treatment, Prognosis and Molecular Pathology of Borderline Ovarian Tumors: Current Status and Perspectives</p>

Abstract

Borderline ovarian tumors (BOTs) are a type of low malignant potential tumor that is typically associated with better outcomes than ovarian cancer. Indeed, its 10-year survival rate is as high as 95%. However, there is a small subset of patients who experience relapse and eventually die. It has been shown that the prognosis of BOTs was based on pathological diagnosis, the age at diagnosis, pre-operative carbohydrate antigen 125 level, invasive implants, and micropapillary patterns. Now the molecular-targeted therapy and molecular-genetic diagnosis have developed into a form of precision medicine. Recent studies on extensive molecular characterizations and molecular pathological mechanisms of BOTs have helped us understand the genomic landscapes of BOTs, and therefore BOTs could be reclassified into biologically and clinically more accurate and effective subtypes. The purpose of this review is to summarize current status for the diagnosis and treatment of BOTs and to describe the research progress on molecular pathologies, with a goal of providing a theoretical perspective for the diagnosis and treatment of BOTs.

Differential gene expression identifies a transcriptional regulatory network involving ER-alpha and PITX1 in invasive epithelial ovarian cancer

“…They generally have an excellent prognosis, with OS only slightly lower than that of the general population [ 15 ]. In general, SBTs are clinically different from LGSOCs [ 16 ], but they share the same KRAS and BRAF mutations [ 15 ], consistent with evidence defining them as precursors of clinically defined LGSOCs [ 17 ]. Whereas most LGSOCs are diagnosed at stage III [ 14 ], the majority of SBTs are detected at stage I [ 18 ].…”

Dysregulated Immunological Functionome and Dysfunctional Metabolic Pathway Recognized for the Pathogenesis of Borderline Ovarian Tumors by Integrative Polygenic Analytics

“…CCR2 can bind with chemokine ligand 2 (CCL2) on macrophages and monocytes to promote the expression and differentiation of T cells and to regulate related inflammatory cytokines by activating the PI3K cascade and small G protein GTPases. CCR2 plays a certain role in the tumorigenesis of ovarian tumors through immune cells and related regulatory responses in the microenvironment, which is also worthwhile to explore in the future [ 17 , 56 , 66 , 67 , 68 , 69 ]. IFNG (IFNγ), the only type II interferon, is an important signal activator of macrophages and inducer of innate and adaptive immunity in accordance with other immune-related cells or cytokines to exert antiproliferative and antitumor effects [ 66 , 70 , 71 ].…”

“…Generally, the 5-year overall survival rates of BOTs for stages I, II, and III are 99, 98, and 96%, respectively, and the 10-year overall survival rates of BOTs for stages I, II, and III are 97, 90, and 88%, respectively [ 14 ]. Nevertheless, some patients with BOTs under primary treatment may suffer from later symptomatic recurrence or malignant transformation resistant to platinum chemotherapy and death even after 20 years [ 15 , 16 , 17 ]. To date, surgery is still the major ideal method to treat BOTs.…”

“…Recent studies have inferenced several assumptions, including the incessant ovulation hypothesis, gonadotropin hypothesis, hormonal hypothesis, and inflammation hypothesis, for the tumorigenesis of BOTs [ 28 , 29 , 30 , 31 ]. Earlier studies for BOTs and their first two most common subtypes, SBOT and MBOT, identified that mutations in the KRAS , BRAF , and ERBB2 genes and overexpression of the p53 and Claudin-1 genes characterized SBOTs and that KRAS mutation, ERBB2 mutation or amplification, trefoil factor-3 (TFF3) strong expression, and HER-2/neu amplification accounted for a certain proportion of MBOT occurrence [ 17 , 32 , 33 , 34 , 35 , 36 , 37 ]. Therefore, detecting the status of KRAS , ERBB2 , p53 , or BRAF mutation status may be a useful way to predict or investigate the possibility and tendency for the recurrence of BOTs or invasive ovarian carcinoma under satisfactory clinical scenarios.…”

“…Therefore, detecting the status of KRAS , ERBB2 , p53 , or BRAF mutation status may be a useful way to predict or investigate the possibility and tendency for the recurrence of BOTs or invasive ovarian carcinoma under satisfactory clinical scenarios. In addition to discovering the position of gene mutations, several preclinical studies have also clarified that several biomolecular activations of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway, PI3K/AKT/mTOR pathway, Hedgehog pathway, and angiogenesis pathway take place in both SBOTs and MBOTs, with certain separate proportions that may appear as targeting subjects for innovative therapies [ 17 , 34 , 38 , 39 , 40 , 41 ]. As a result, clinical trials for low-grade serous carcinoma, mucinous carcinoma, and BOTs with targeted therapies focused on potential genes or pathways mentioned above have developed slowly and gradually in recent years, including MEK inhibitor (MEKi) therapy, agents targeting the PI3K/AKT/mTOR pathway, and antiangiogenic agents.…”