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Objective Advanced stage mucinous ovarian cancers are diagnostically and therapeutically challenging. Histotype specific trials have failed due to low recruitment after excluding non-ovarian primaries. Mucinous ovarian cancers are commonly metastatic from other sites however lack definitive diagnostic markers. We suggest a classification of mucinous ovarian cancers of uncertain primary origin ‘MO-CUPs’ in clinical trials. This study aims to identify drug targets to guide treatment and future trials. Methods We analyzed a large de-identified, multi-platform tumor profiling dataset of MO-CUPs enriched for advanced stage and recurrent cases submitted to Caris Life Sciences. Available data included a 45-gene next-generation sequencing (NGS) panel, gene amplification of HER2 and cMET and 18 immunohistochemical (IHC) markers of drug sensitivity/resistance. Results Mucinous tumors from 333 patients were analyzed, including 38 borderline tumors and 295 invasive cancers. The most common mutations in a subset (n = 128) of invasive cancers were KRAS (60%), TP53 (38%), PIK3CA (13%) and PTEN (9%). Borderline tumors had higher rates of BRAF mutations, and PGP and TOP2A overexpression than invasive cases. KRAS mutant invasive cancers had lower expression of thymidylate synthase (p = 0.01) and higher expression of TUBB3 (p = 0.01) than KRAS wildtype tumors. Conclusions To our knowledge, this is the largest series profiling mucinous ovarian cancers and almost certainly includes cases of ovarian and non-ovarian origin. Given the difficulty recruiting patients to histotype-specific trials in rare subsets of ovarian cancer, it may be more important to focus on identifying potential treatment targets and to personalise treatment and design clinical trials in MO-CUPS agnostic of primary site to overcome these issues. [ABSTRACT FROM AUTHOR]

The early detection of ovarian cancer is critical for improving the prognosis of patients, but there are currently insufficient tumor biomarkers for early detection owing to their low diagnostic sensitivity and specificity. The aim of the present study was to investigate the use of the serum antigens C‑C motif chemokine ligand 18 and C‑X‑C motif chemokine ligand 1, and autoantibodies C1D, transmembrane 4 L six family member 1, zinc finger protein 675 and fragile X mental retardation 1 autosomal homolog 1, for the early screening of epithelial ovarian cancer (EOC). The expression of these sex genes/proteins in ovarian cancer and normal ovarian tissue was examined, and the potential functions of the six genes/proteins in ovarian cancer were analyzed by bioinformatics. Finally, these data were verified in clinical samples, and the multi‑analyte suspension array method was compared with the ELISA method. Taken together, these data indicated that these six genes/proteins may serve as potential biomarkers for the early detection of EOC. [ABSTRACT FROM AUTHOR]

Abstract: Background: To compare the survival impact of several lymph node staging methods and therapeutic role of lymphadenectomy in patients with epithelial ovarian cancer who had undergone lymphadenectomy. Methods: Data were retrospectively collected from the Surveillance, Epidemiology, and End Results program between 1988 and 2013. Results: An increasing number of resected lymph nodes (RLNs) was associated with a significant improvement in survival of FIGO stage II and III disease. However, for FIGO stage IV patients, better survival was not significantly associated with a more extensive lymphadenectomy. A higher lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS) were associated with poorer survival regardless of stage. Nevertheless, four‐category classification of LODDS was more suitable for stage IV patients when three‐category classification was compatible with stage I‐III disease. Multivariate analysis demonstrated that LODDS and LNR were significant independent prognostic factors, but not RLN classification. Conclusion: Sixteen to thirty RLNs are recommended for stage I disease. For stages II and III patients, the more lymph node excision, the better the prognosis. However, lymphadenectomy was nonessential for stage IV patients. Considering staging methods, for stages II and III patients, three‐category classification of LODDS was recommended to evaluate the prognosis. For stage I and IV, three‐category classification of positive LNR was idoneous. [ABSTRACT FROM AUTHOR]

Highlights • We tackle the problem of early detection of ovariance cancer using longitudinal measurements of multiple biomarkers. • We compare two different paradigms: Bayesian methods and deep learning. • We provide evidence that using multiple biomarkers yields a performance boost as compared to the standard screening test using CA125 alone. Abstract We present a quantitative study of the performance of two automatic methods for the early detection of ovarian cancer that can exploit longitudinal measurements of multiple biomarkers. The study is carried out for a subset of the data collected in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). We use statistical analysis techniques, such as the area under the Receiver Operating Characteristic (ROC) curve, for evaluating the performance of two techniques that aim at the classification of subjects as either healthy or suffering from the disease using time-series of multiple biomarkers as inputs. The first method relies on a Bayesian hierarchical model that establishes connections within a set of clinically interpretable parameters. The second technique is a purely discriminative method that employs a recurrent neural network (RNN) for the binary classification of the inputs. For the available dataset, the performance of the two detection schemes is similar (the area under ROC curve is 0.98 for the combination of three biomarkers) and the Bayesian approach has the advantage that its outputs (parameters estimates and their uncertainty) can be further analysed by a clinical expert. [ABSTRACT FROM AUTHOR]

Objectives The current study aimed to investigate FSH receptor binding inhibitor (FRBI) effects in the expressions of FSH receptor (FSHR) and estrogen receptor-beta (ERβ) in the mice ovaries at the gene and protein levels, also to find the potential efficacy of FRBI on suppressing ovarian cancer through down-regulating over-expression of FSHR and ERβ in the normal ovarian tissues. Methods 180 female mice were randomized into six groups ( n  = 30). Mice of FRBI-1, FRBI-2 and FRBI-3, FRBI-4 were intramuscularly injected with FRBI of 10, 20, 30 and 40 mg/kg, respectively, for five consecutive days. The qPCR and Western blotting were used to determine expression levels of FSHR and ERβ mRNAs and proteins in mouse ovaries. Results The ovarian cortex thickness (OCT) of the FRBI-4 group were less than that FSH group on day 30 ( P  < 0.05). The numbers of secondary follicles (SF) and the maximum transverse diameters (MTD) of secondary follicles of FRBI-3 and FRBI-4 groups were decreased as compared to FSH group ( P  < 0.05 or P  < 0.01) by 24.11% and 27.47% on day 20 based on the control group (CG) levels. On day 15, the reductions of FSHR mRNA levels in FRBI-2, FRBI-3 and FRBI-4 were 27.78%, 29.37% and 43.65% ( P  < 0.05 or P  < 0.01), respectively in comparison with CG. ERβ and FSHR protein levels of FRBI-treated mice were gradually decreased as compared to and CG and FSH group. ERβ protein level of FRBI-4 was less than that of CG on day 20 ( P  < 0.05). On days 15 and 20, estradiol (E 2 ) concentrations of FRBI-2, FRBI-3 and FRBI-4 groups were lower than those of the CG and FSH group ( P  < 0.05 or P  < 0.01). Conclusions FRBI could reduce OCT and follicle numbers. A high dose of FRBI (30 mg/kg to 40 mg/kg) could suppress ovarian and follicular development, and attenuate expression levels of ERβ and FSHR mRNAs and proteins in the ovaries, additionally inhibit E 2 production. Therefore, FRBI will possibly be utilized to restrain the carcinogenesis of ovarian cancer by down-regulating overexpression of FSHR and ERβ in the ovaries. [ABSTRACT FROM AUTHOR]

Objective To describe clinical characteristics of Lynch syndrome associated ovarian cancer and the efficacy of surveillance in the early detection of these ovarian cancers. Methods All Lynch syndrome associated ovarian cancer cases identified in either the Dutch Lynch syndrome registry (DLSR) between 1987 and 2016, and/or the cohort at the University Medical Center Groningen (UMCG) between 1993 and 2016 were included. Clinical data on age at diagnosis, mutation type, histological type, FIGO stage, treatment, follow-up and gynecological surveillance were collected. Results A total of 46/798 (6%) women in the DLSR and 7/80 (9%) in the UMCG cohort were identified as LS associated ovarian cancer patients. The median age at ovarian cancer diagnosis was 46.0 years (range 20–75 years). The most frequently reported histological type was endometrioid adenocarcinoma (40%; n  = 21) and serous carcinoma (36%; n  = 19). Most tumors (87%; n  = 46) were detected at an early stage (FIGO I/II). Forty-one of 53 (77%) patients were diagnosed with ovarian cancer before LS was diagnosed. In the other 12/53 (23%) women, ovarian cancer developed after starting annual gynecological surveillance for LS; three ovarian cancers were screen-detected in asymptomatic women. Overall survival was 83%. Conclusion Ovarian cancer in women with LS has a wide age-range of onset, is usually diagnosed at an early stage with predominantly endometrioid type histology and a good overall survival. The early stage at diagnosis could not be attributed to annual gynecological surveillance. [ABSTRACT FROM AUTHOR]

Purpose: To investigate magnetic resonance (MR) findings and to detect malignant transformation of ovarian endometriotic cysts by comparing longitudinal changes in patients with ovarian malignant/borderline tumors associated with ovarian endometriotic cysts (tumor group) with those of patients with endometriotic cysts (control group).Methods: Tumor group patients (n = 10) had ovarian malignant/borderline tumors with pathologically confirmed association with endometriosis and available prior MRI of endometriotic cysts. Control group patients (n = 40) had been diagnosed more than two times as having ovarian endometriotic cysts by MRI examination. The tumor and solid portion sizes were measured. Two radiologists independently evaluated signal intensity (SI) of the cystic portion on both T1-weighted and T2-weighted images (WI), presence of shading on T2WI, and T2 dark spot sign in both groups and evaluate longitudinal changes of those findings.Results: Pathological diagnoses of the tumor group were clear cell carcinoma (n = 6), endometrioid carcinoma (n = 1), serous carcinoma (n = 1), mucinous borderline tumor (n = 1), and endometrioid borderline tumor (n = 1). Tumor size had increased significantly in the tumor group (p = .004), but not in controls. Solid portions were identified in all cases only when neoplasms were suspected. Disappearance of shading during the follow-up period was observed more in tumor group (n = 2) than in the controls (n = 0). No significant difference was found between groups in the SI on T1 and T2WI, and T2 dark spot sign for the two MR examinations.Conclusions: The MR findings suggesting malignant transformation were emergence of a solid portion and increase in cyst size. Disappearance of shading also facilitates the follow-up of endometriotic cysts. [ABSTRACT FROM AUTHOR]

The current lack of an accurate, cost-effective and non-invasive test that would allow for screening and diagnosis of gynaecological carcinomas, such as endometrial and ovarian cancer, signals the necessity for alternative approaches. The potential of spectroscopic techniques in disease investigation and diagnosis has been previously demonstrated. Here, we used attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy to analyse urine samples from women with endometrial (n = 10) and ovarian cancer (n = 10), as well as from healthy individuals (n = 10). After applying multivariate analysis and classification algorithms, biomarkers of disease were pointed out and high levels of accuracy were achieved for both endometrial (95% sensitivity, 100% specificity; accuracy: 95%) and ovarian cancer (100% sensitivity, 96.3% specificity; accuracy 100%). The efficacy of this approach, in combination with the non-invasive method for urine collection, suggest a potential diagnostic tool for endometrial and ovarian cancers. [ABSTRACT FROM AUTHOR]

Since after 2006 when the first edition of practice guidelines for gynecologic oncologic cancer treatment was released, the Korean Society of Gynecologic Oncology (KSGO) has published the following editions on a regular basis to suggest the best possible standard care considering updated scientific evidence as well as medical environment including insurance coverage. The Guidelines Revision Committee was summoned to revise the second edition of KSGO practice guidelines, which was published in July 2010, and develop the third edition. The current guidelines cover strategies for diagnosis and treatment of primary and recurrent ovarian cancer. In this edition, we introduced an advanced format based on evidence-based medicine, collecting up-to-date data mainly from MEDLINE, EMBASE, and Cochrane Library CENTRAL, and conducting a meta-analysis with systematic review. Eight key questions were raised by the committee members. For every key question, recommendations were developed by the consensus meetings and provided with evidence level and strength of the recommendation. [ABSTRACT FROM AUTHOR]

Objective: The choice between primary debulking surgery (PDS) and neoadjuvant chemotherapy (NAC) in advanced ovarian cancer remains controversial. We evaluated NAC use in our center before and after results from a randomized trial were published, with the aim to determine the impact of changes in the neoadjuvant strategy on survival in advancedstage ovarian cancer. Methods: We retrospectively investigated the clinical course of 435 patients with ovarian, tubal, or peritoneal carcinoma (International Federation of Gynecology and Obstetrics [FIGO] stage III or IV). According to the period of treatment, we stratified patients into a control group (n=216; diagnosed between 2006 and 2010; 83.8% underwent PDS) and a study group (n=219; diagnosed between 2011 and 2014; 48.9% received NAC followed by interval debulking surgery [IDS]). Results: There were no between-group differences in age, body mass index, histology findings, or tumor grade. Compared to patients in the control group, those in the study group were more likely to receive NAC followed by IDS as first-line treatment (48.9% vs. 16.2%; p<0.001), cytoreductive surgery to no-residual disease (21.5% vs. 10.2%; p<0.001), or radical surgery (57.5% vs. 35.6%; p<0.001). However, there was no between-group difference in postoperative morbidity. Kaplan-Meier analysis showed no between-group differences in progression-free or overall survival (p=0.449 and 0.952, respectively). Conclusion: NAC incorporation resulted in increased optimal cytoreduction rates although no significant differences in survival outcomes were noted. NAC is advantageous for patients with high perioperative morbidity or unresectable disease. [ABSTRACT FROM AUTHOR]

Objective Mucinous ovarian cancer (MOC) is a rare type of epithelial ovarian cancer resistant to standard chemotherapy regimens. We sought to characterize the repertoire of somatic mutations in MOCs and to define the contribution of massively parallel sequencing to the classification of tumors diagnosed as primary MOCs. Methods Following gynecologic pathology and chart review, DNA samples obtained from primary MOCs and matched normal tissues/blood were subjected to whole-exome ( n  = 9) or massively parallel sequencing targeting 341 cancer genes ( n  = 15). Immunohistochemical analysis of estrogen receptor, progesterone receptor, PTEN, ARID1A/BAF250a, and the DNA mismatch (MMR) proteins MSH6 and PMS2 was performed for all cases. Mutational frequencies of MOCs were compared to those of high-grade serous ovarian cancers (HGSOCs) and mucinous tumors from other sites. Results MOCs were heterogeneous at the genetic level, frequently harboring TP53 (75%) mutations, KRAS (71%) mutations and/or CDKN2A / B homozygous deletions/mutations (33%). Although established criteria for diagnosis were employed, four cases harbored mutational and immunohistochemical profiles similar to those of endometrioid carcinomas, and one case for colorectal or endometrioid carcinoma. Significant differences in the frequencies of KRAS , TP53 , CDKN2A , FBXW7 , PIK3CA and/or APC mutations between the confirmed primary MOCs ( n  = 19) and HGSOCs, mucinous gastric and/or mucinous colorectal carcinomas were found, whereas no differences in the 341 genes studied between MOCs and mucinous pancreatic carcinomas were identified. Conclusions Our findings suggest that the assessment of mutations affecting TP53 , KRAS , PIK3CA , ARID1A and POLE , and DNA MMR protein expression may be used to further aid the diagnosis and treatment decision-making of primary MOC. [ABSTRACT FROM AUTHOR]

Objectives For women at high risk of developing ovarian cancer, it is important to provide an accurate recommendation for the optimal age for preventive surgery in order to maximize the preventative effect while delaying symptoms associated with early surgical menopause. The goal of the current study was to estimate age-specific incidence rates of ovarian cancer among women with a BRCA1 or BRCA2 mutation. Methods From our international registry, we identified 5689 women with no previous diagnosis of ovarian or fallopian tube cancer or preventive oophorectomy. Women were followed from the date of completion of the baseline questionnaire until either a diagnosis of ovarian or fallopian tube cancer, prophylactic oophorectomy, death or last follow-up. The annual and cumulative incidence rates of ovarian cancer were estimated. Results Over a mean follow-up period of 4.7 years (ranges 0–22.6), 195 incident ovarian or fallopian tube cancers were diagnosed (169 [86%] ovarian cancers, 22 [11%] fallopian tube cancers and four [2%] cancers that involved both the ovaries and fallopian tubes). Of these, 45 (23%) cancers were diagnosed at preventive surgery (occult cancers). The cumulative risk of ovarian cancer to age 80 was 49% for BRCA1 and 21% for BRCA2 mutation carriers. The mean age at diagnosis was 51.3 years (ranges 33–84) among women with a BRCA1 mutation and 61.4 years (ranges 44–80) among women with a BRCA2 mutation. Conclusion Based on a cumulative risk of 0.55% to age 35 for BRCA1 mutation carriers and of 0.56% to age 45 for BRCA2 mutation carriers, we recommend bilateral salpingo-oophorectomy before age 40, but ideally by age 35, for women with a BRCA1 mutation and by age 45 for those with a BRCA2 mutation to maximize prevention and to minimize adverse effects. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate stereotactic body radiation therapy (SBRT) for metachronous oligometastatic ovarian cancer patients in terms of local control, delay of systemic treatment, survival outcomes, and toxicity.Methods and Materials: Retrospective data collection from a single institution was performed. The inclusion criteria were as follows: (1) oligorecurrent or oligoprogressive disease in ovarian cancer patients during or after systemic therapy; (2) surgery or other local therapies not feasible; and (3) relative contraindication to systemic therapy for reasons such as unavailability of additional chemotherapy lines or refusal of the patient. Tumor response and toxicity were evaluated using the Response Evaluation Criteria in Solid Tumors and the Common Terminology Criteria for Adverse Events version 4.03, respectively. A new systemic therapy regimen was started after an SBRT treatment course in 57 of 109 cases (52.3%). Local progression-free survival, progression-free survival, and overall survival were calculated via the Kaplan-Meier method. The systemic treatment-free interval was calculated in cases without concomitant systemic therapy.Results: Between May 2012 and December 2016, 82 patients (156 lesions) underwent SBRT with a median dose of 24 Gy in 3 fractions. The median follow-up period was 17.4 months. Patients received a median of 3 systemic therapy regimens prior to SBRT. Concomitant systemic therapy was performed for 29 lesions (18.6%). Among 152 evaluable lesions, a complete radiologic response, partial response, stabilization, and progressive disease were observed in 91 (60%), 26 (17%), 24 (16%), and 11 (7%), respectively. No grade 3 or 4 acute or late toxicities were observed. The median systemic treatment-free interval after SBRT was 7.4 months, and 1 of 3 patients was disease free at 1 year after SBRT. The actuarial 2-year local progression-free survival, progression-free survival, and overall survival rates were 68%, 18%, and 71%, respectively. The pattern of failure was predominantly out of field.Conclusions: SBRT for oligometastatic ovarian cancer showed good local control and a good toxicity profile. It might be an appealing alternative to other invasive local therapies to delay systemic therapy in the case of chemorefractory disease or intolerance to systemic agents. [ABSTRACT FROM AUTHOR]

This article reviews the emerging roles of functional imaging in the assessment of peritoneal carcinomatosis in ovarian cancer, focusing on the use of diffusion-weighted magnetic resonance imaging (DW-MRI) and 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography combined with computed tomography (PET-CT), their advantages and shortcomings as well as the added-value over conventional imaging. [ABSTRACT FROM AUTHOR]

In recent decades, numerous long non-coding (lnc)RNAs, including growth arrest-specific transcript 5 (GAS5), have been demonstrated to exert promoting or suppressive effects in human cancers. Decreased expression of the lncRNA GAS5 was reported to promote cell proliferation, migration and invasion and indicate poor prognosis in ovarian cancer. However, the exact underlying molecular mechanism through which GAS5 is involved in ovarian cancer growth remains unknown. The present study aimed to investigate the regulatory mechanism of GAS5 in ovarian cancer cell proliferation. Quantitative polymerase chain reaction and western blot analysis were used to examine RNA and protein expression, respectively. An MTT assay was used to examine cell proliferation. A luciferase reporter gene assay was conducted to verify the targeting relationship. It was identified that the expression levels of GAS5 and Sprouty homolog 2 (SPRY2) were significantly downregulated, while the expression level of microRNA (miR)-21 was significantly upregulated in ovarian cancer tissues and cell lines compared with adjacent non-tumor tissues and normal ovarian epithelial cells, respectively. Downregulation of GAS5 was significantly associated with advanced clinical stage. Luciferase assay data indicated that miR-21 was a direct target of GAS5 and that SPRY2 was a target gene of miR-21 in ovarian cancer-derived A2780 cells. GAS5 overexpression significantly inhibited the proliferation of ovarian cancer cells, which was accompanied by the downregulation of miR-21 and the upregulation of SPRY2. The overexpression of miR-21 caused a significant decrease in A2780 cell proliferation, which was accompanied by reduced SPRY2 expression. Furthermore, miR-21 overexpression attenuated the suppressive effects of GAS5 on A2780 cell proliferation and rescued the promoting effects of GAS5 on SPRY2 expression. In addition, the knockdown of SPRY2 also rescued the suppressive effects of GAS5 on the proliferation of A2780 cells. In summary, our study demonstrates that GAS5 exerts a suppressive effect on the proliferation of ovarian cancer cells, at least in part via the inhibition of miR-21 expression and subsequent increased SPRY2 expression. These findings suggest that the GAS5/miR-21/SPRY2 signaling pathway may be a potential therapeutic target in ovarian cancer. [ABSTRACT FROM AUTHOR]

Purpose We sought to develop a matrix assisted laser desorption ionization-time of flight (MALDITOF)- based, ovarian cancer (OVC), low-mass-ion discriminant equation (LOME) and to evaluate a possible supportive role for triple-TOF mass analysis in identifying metabolic biomarkers. Materials and Methods A total of 114 serum samples from patients with OVC and benign ovarian tumors were subjected to MALDI-TOF analysis and a total of 137 serum samples from healthy female individuals and patients with OVC, colorectal cancer, hepatobiliary cancer, and pancreatic cancer were subjected to triple-TOF analysis. An OVC LOME was constructed by reference to the peak intensity ratios of discriminatory low-mass ion (LMI) pairs. Triple-TOF analysis was used to select and identify metabolic biomarkers for OVC screening. Results Three OVC LOMEs were finally constructed using discriminatory LMI pairs (137.1690 and 84.4119 m/z; 496.5022 and 709.7642 m/z; and 524.5614 and 709.7642 m/z); all afforded accuracies of > 90%. The LMIs at 496.5022 m/z and 524.5614 m/z were those of lysophosphatidylcholine (LPC) 16:0 and LPC 18:0. Triple-TOF analysis selected seven discriminative LMIs; each LMI had a specificity > 90%. Of the seven LMIs, four with a 137.0455 m/z ion at retention times of 2.04-3.14 minutes were upregulated in sera from OVC patients; the ion was identified as that derived from hypoxanthine. Conclusion MALDI-TOF-based OVC LOMEs combined with triple-TOF-based OVC metabolic biomarkers allow reliable OVC screening; the techniques are mutually complementary both quantitatively and qualitatively. [ABSTRACT FROM AUTHOR]

Normal-sized ovarian carcinoma syndrome (NOCS) is a rare condition characterised by malignancy identified in ovaries of normal size with abdominal metastasis. We report two cases of advanced ovarian carcinoma with ovaries of normal size. The first case was a 13-year-old adolescent with malignant ascites and bilateral normal sized multicystic ovaries detected on ultrasound. Serum cancer antigen 125 (CA 125) and lactate dehydrogenase were markedly raised. A computed tomography (CT) scan showed the presence of thick omental cake but no ovarian tumour. An ultrasound-guided biopsy of the omental cake was undertaken. A histopathological examination and immunohistochemical studies of omentum caking confirmed a diagnosis of high-grade serous carcinoma of ovarian in origin. Despite neoadjuvant chemotherapy, she deteriorated rapidly with acute renal failure and respiratory distress. She succumbed to her disease 10 weeks after diagnosis. The second case, a 69-year-old postmenopausal female presented with malignant ascites and ultrasound evaluation showed hydrometra and bilateral atrophic ovaries. CA 125 was significantly raised. A laparoscopic biopsy of the left ovary and endometrial sampling were performed. A diagnosis of synchronous primary high grade papillary serous ovarian cystadenocarcinoma and endometrial adenocarcinoma were revealed. Relapse occurred despite ongoing adjuvant chemotherapy. We concluded that a preoperative definitive diagnosis of NOCS is difficult. Strong clinical suspicion is needed when all the important causes of malignant ascites are excluded. Radiologicalguided biopsy and laparoscopic biopsy are useful to achieve the diagnosis of NOCS. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to evaluate the performance of human epididymal protein 4 (HE4), cancer antigen 125 (CA 125) and a combination of both via the Risk of Ovarian Malignancy Algorithm (ROMA) in detecting ovarian malignancy. Methods: This was a diagnostic study enrolling 129 patients with pelvic mass(es) suspected of originating in the ovary who had been scheduled for surgery or radiological-guided biopsy. Serum HE4 and CA 125 levels were measured. HE4, CA 125 and ROMA were evaluated for sensitivity, specificity, positive predictive value and negative predictive value. The receiver operating characteristic (ROC) plots were graphed and area under the curve (AUC) values were calculated to investigate the accuracy of each marker for predicting ovarian malignancy. Results: Overall, CA 125 remained significantly more sensitive (88.9% vs. 51.9%, p = 0.006) but less specific (56.9% vs. 95.1%, p < 0.001) than HE4. HE4 was superior to CA 125 in specificity (97.7% vs. 54.5%, p < 0.001) for premenopausal women. ROMA was non-significantly more sensitive (100.0% vs. 92.3%, p = 1.000) than CA 125 but both were equally specific (71.4%) for the postmenopausal group. In the premenopausal group, the AUC of serum HE4 was higher than serum CA 125 (0.851 vs. 0.817) but was equivalent to ROMA (0.851 vs. 0.859). In the postmenopausal group, ROMA exhibited an excellent AUC value as compared to CA 125 and HE4 (AUC of 0.907 vs. 0.874 vs. 0.863, respectively). Conclusion: HE4 is useful in ruling out ovarian malignancy among premenopausal women. For postmenopausal women, ROMA appears to be an all-rounder with overall good sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OVC) is the most lethal of the gynecological malignancies, with diagnosis often occurring during advanced stages of the disease. Moreover, a majority of cases become refractory to chemotherapeutic approaches. Therefore, it is important to improve our understanding of the molecular dependencies underlying the disease to identify novel diagnostic and precision therapeutics for OVC. Cancer cells are known to sequester iron, which can potentiate cancer progression through mechanisms that have not yet been completely elucidated. We developed an algorithm to identify novel links between iron and pathways implicated in high-grade serous ovarian cancer (HGSOC), the most common and deadliest subtype of OVC, using microarray gene expression data from both clinical sources and an experimental model. Using our approach, we identified several links between fatty acid (FA) and iron metabolism, and subsequently developed a network for iron involvement in FA metabolism in HGSOC. FA import and synthesis pathways are upregulated in HGSOC and other cancers, but a link between these processes and iron-related genes has not yet been identified. We used the network to derive hypotheses of specific mechanisms by which iron and iron-related genes impact and interact with FA metabolic pathways to promote tumorigenesis. These results suggest a novel mechanism by which iron sequestration by cancer cells can potentiate cancer progression, and may provide novel targets for use in diagnosis and/or treatment of HGSOC. [ABSTRACT FROM AUTHOR]

Background: Characterization of an ovarian lesion represents a diagnostic challenge; the optimal assessment of an adnexal mass requires a multidisciplinary approach, based on physical examination, laboratory tests and imaging techniques. Diagnostic imaging plays a crucial role in detection, characterization and staging of adnexal masses. Magnetic Resonance Imaging (MRI) is an essential problem solving tool to determine the site of origin of a pelvic mass and then to characterize an adnexal mass, especially in patients with indeterminate lesions. Aim of the Work: The aim of the study is to evaluate role of MRI as a powerful and noninvasive technique which may effectively characterize and differentiate between various suspicious ovarian lesions. Patients and Methods: The current study is a prospective analysis that evaluated 26 female patients with 36 suspicious ovarian lesions. The study was conducted at Radiology Department of El-Demerdash hospital. The patients were previously evaluated by ultrasound examination in the period from November 2017 to April 2018. The patients' age ranged from 12 to 65 years old (mean age 41± 15 SD). 4 patients presented by abdominal swelling (15%), 8 were complaining of chronic pelvic pain (30.7%), 10 came with menstrual irregularities (38%) and 4 (15%) cases were accidentally discovered during US examination. Results: This study included 36 ovarian lesions in 26 patients (8 cases had bilateral masses). The age in cases with benign lesions ranged from 12 to 65 years (Mean age 37.31 ± 16.214 SD), While the age in cases with malignant lesions; ranged from 14 to 61 years. (Mean age 44.38±14.015 SD) . Conclusion: As an advanced technique, dynamic contrast-enhanced MRI (DCE-MRI) plays an important role in tumor detection and characterization, subtyping, prediction of prognosis, treatment monitoring, and drug development. [ABSTRACT FROM AUTHOR]

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Ovarian cancer is one of the most common gynecologic malignancies. Accurate classification of ovarian cancer types (serous carcinoma, mucous carcinoma, endometrioid carcinoma, transparent cell carcinoma) is an essential part in the different diagnosis. Computer-aided diagnosis (CADx) can provide useful advice for pathologists to determine the diagnosis correctly. In our study, we employed a Deep Convolutional Neural Networks (DCNN) based on AlexNet to automatically classify the different types of ovarian cancers from cytological images. The DCNN consists of five convolutional layers, three max pooling layers, and two full reconnect layers. Then we trained the model by two group input data separately, one was original image data and the other one was augmented image data including image enhancement and image rotation. The testing results are obtained by the method of 10-fold cross-validation, showing that the accuracy of classification models has been improved from 72.76 to 78.20% by using augmented images as training data. The developed scheme was useful for classifying ovarian cancers from cytological images. [ABSTRACT FROM AUTHOR]

Malignant ovarian tumors occur at all ages, including early childhood, but also advanced old age, with the total incidence dramatically increasing with age. Tumor markers for early detection of ovarian carcinoma are used in ovarian cancer examination. The aim of the study was to examine the degree of correlation between sonographic findings and the levels of serum tumor marker Ca 125, and to study a correlation of preoperative sonographic findings and serum marker level CA 125 with intraoperative finding and patohistopathological results. The study was based on the prospective-retrospective study model involving 60 postmenopausal women diagnosed with the presence of ovarian tumor. The following medical tests and examinations were performed for all patients: anamnestic analysis of the medical record, that is the history of the disease with the data on age, parity, duration of menopause, the use of oral contraceptives and symptomatology, small pelvis sonography, lab parameters - Ca 125 with referent ranges up to 35 ml/U. Laparotomy was used as an operative procedure in all patients. All material obtained operatively underwent histopathological treatment. The group of patients with malignant tumors of high statistical significance showed considerably higher average CA125 values. Among subjects with benign tumors, the dominant tumor structure was cystic, as opposed to the mixed-type tumors in malignant tumors. To this effect, the parameter of tumor structure is a serious factor in distinguishing between benign and malignant ovarian tumors. Tumor location is, with high statistical significance, more often bilateral in subjects with histopathologically proven malignant tumors, while it is predominantly unilateral in benign tumors. [ABSTRACT FROM AUTHOR]

Remodeling of the extracellular matrix in human ovarian cancer can be manifested in increased collagen concentration, changes in alignment within fibrils/fibers and/or up-regulation of different collagen isoforms. We used pixel-based second harmonic generation (SHG) polarization microscopy analyses to probe these molecular changes in human ovarian tissues [normal stroma, benign tumors, and high-grade serous (HGS) tumors] by: (i) determination of the α-helical pitch angle via the single-axis molecular model, (ii) collagen alignment within fibrils via SHG anisotropy, and (iii) chirality via SHG circular dichroism (SHG-CD). Pixel approaches are required due to the complex structure of the matrix that lacks a high degree of fiber alignment. The largest differences in the helical pitch angle were between normal stroma and benign tumors, consistent with gene expression showing the Col III isoform is up-regulated in the latter. The data were not consistent with up-regulation of Col III in HGS tumors as previous reports have suggested. The different tissues also displayed differing SHG anisotropies and SHG-CD responses, consistent with either Col III incorporation or randomization of Col I alignment within benign and malignant tumors. Additionally, the high-grade tumors displayed higher collagen concentration, where this desmoplasia is consistent with the higher fiber density in these tissues. These results collectively indicate that the fibril assemblies are distinct in all tissues, where these differences likely result from the synthesis of collagen rather than remodeling of existing collagen. Importantly, these analyses are label-free and interrogate subresolution collagen structure on intact tissues, without the need for conventional structural biology tools. [ABSTRACT FROM AUTHOR]

Histopathological image analysis of stained tissue slides is routinely used in tumor detection and classification. However, diagnosis requires a highly trained pathologist and can thus be time-consuming, labor-intensive, and potentially risk bias. Here, we demonstrate a potential complementary approach for diagnosis. We show that multiphoton microscopy images from unstained, reproductive tissues can be robustly classified using deep learning techniques. We fine-train four pretrained convolutional neural networks using over 200 murine tissue images based on combined second-harmonic generation and two-photon excitation fluorescence contrast, to classify the tissues either as healthy or associated with high-grade serous carcinoma with over 95% sensitivity and 97% specificity. Our approach shows promise for applications involving automated disease diagnosis. It could also be readily applied to other tissues, diseases, and related classification problems. [ABSTRACT FROM AUTHOR]

Purpose: To investigate rural-metropolitan disparities in ovarian cancer survival, we assessed ovarian cancer mortality and differences in prognostic factors by rural-metropolitan residence.Methods: The Utah Population Database was used to identify ovarian cancer cases diagnosed between 1997 and 2012. Residential location information at the time of cancer diagnosis was used to stratify rural-metropolitan residence. All-cause death and ovarian cancer death risks were estimated using Cox proportional hazard regression models.Results: Among 1661 patients diagnosed with ovarian cancer, 11.8% were living in rural counties of Utah. Although ovarian cancer patients residing in rural counties had different characteristics compared with metropolitan residents, we did not observe an association between rural residence and risk of all-cause nor ovarian cancer-specific death after adjusting for confounders. However, among rural residents, ovarian cancer mortality risk was very high in older age at diagnosis and for mucinous carcinoma, and low in overweight at baseline.Conclusions: Rural residence was not significantly associated with the risk of ovarian cancer death. Nevertheless, patients residing in rural-metropolitan areas had different factors affecting the risk of all-cause mortality and cancer-specific death. Further research is needed to quantify how mortality risk can differ by residential location accounting for degree of health care access and lifestyle-related factors. [ABSTRACT FROM AUTHOR]

BACKGROUND: Aberrant DNA methylation of protocadherins (PCDHs) has been associated with development and progression of various types of cancer. It could represent possible direction in the search for critically needed tumor biomarkers for ovarian cancer. OBJECTIVE: To investigate methylation of δ 2 group of non-clustered PCDHs in high-grade serous ovarian carcinoma (HGSOC) tissue in comparison with control tissue. METHODS: We used next-generation sequencing for detecting regions with the most altered methylation. For further confirmation of discovered alterations we used methylation-sensitive high-resolution melting analysis. RESULTS: PCDH17 methylation was detected in almost 70% of HGSOC patients without any methylation in the group of control samples and was found both in the late stage tumors as well as in the early stage ones. Other selected PCDHs did not show any relevant changes in methylation. Subsequent gene expression analysis of PCDH17 revealed decreased expression in all of the tumor samples in comparison to the control ones. Statistically significant negative correlation was found between methylation and levels of expression suggesting potentially methylation-based silencing. CONCLUSIONS: Methylation of PCDH17 could play an important role in development and progression of HGSOC and has potential to become a target in the search for new clinical biomarkers. [ABSTRACT FROM AUTHOR]

Ovarian cancer is a low-prevalence postmenopausal cancer with a high mortality rate and is the fifth most lethal cancer in women. The most common serous subtype with TP53 mutations spreads rapidly throughout the peritoneal cavity (stage III/IV) when 5-year survival is 10%. If diagnosed while confined to the ovary (stage I), the survival rate exceeds 90%. This is the rationale for screening. Annual transvaginal ultrasound (TVU) scans used as a primary screening modality or as a second-line test following primary screening with serum CA125 (multimodal) have been investigated in several trials. Only two large randomized controlled trials have provided mortality data. The US Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial studied over 78 000 women (randomized to screening with either TVU or CA125, or control) over 6 years with 14 years follow-up and found no mortality benefit from screening and increased morbidity in the screened arm. The UK Collaborative Trial of Ovarian Cancer Screening studied over 202 000 women randomized to TVU, multimodal or control in a 1 : 1 : 2 ratio over 7-11 years with 11 years follow-up. CA125 was interpreted by the Risk of Ovarian Cancer algorithm which identifies a rise in the level rather than a fixed cut-off. There was a late reduction in mortality after 7 years in the screened arm (23% in the multimodal arm and 21% in the TVU arm), but the overall reduction was not significant. Further follow-up may reveal whether TVU has a primary or secondary role in ovarian cancer screening. [ABSTRACT FROM AUTHOR]

Ovarian cancer is a markedly heterogeneous malignancy characterized by various histological subtypes. Molecular biomarkers have been indicated to serve significant functions in the early diagnosis and treatment of early‑stage ovarian cancer. However, the detailed mechanism underlying the tumorigenesis of ovarian cancer remains unclear. The present study aimed to identify a novel long non‑coding RNA in patients with ovarian cancer. Nicotinamide nucleotide transhydrogenase‑antisense 1 (NNT‑AS1) was markedly downregulated in patients with ovarian cancer and in cultured human ovarian cancer cells. Knockdown of NNT‑AS1 in the human ovarian cancer cell lines HO‑8910 and SK‑OV‑3 promoted colony formation and arrested the cell cycle at G0/G1 phase. Furthermore, Transwell demonstrated that the down regulation of NNT‑AS1 increased cell migration and invasion by ~60 and 70%, respectively, in HO‑8910 and SK‑OV‑3 cells. Furthermore, cell apoptosis was inhibited by the transfection of siNNT‑AS1 in the two cell lines, whereas the relative activities of caspase‑3 and caspase‑9 were decreased. These results indicated a protective function of NNT‑AS1 in human ovarian cancer, providing novel insights into the diagnosis and treatment of ovarian cancer in clinical settings. [ABSTRACT FROM AUTHOR]

Cisplatin‑resistant ovarian cancer occurs in patients with ovarian cancer treated with cisplatin‑based chemotherapy, which results in tumor progression during treatment, or recurrence of the tumor within 6 months of the treatment. It is vital that a novel biomarker for diagnosis, or an efficient therapeutic target of cisplatin‑resistant ovarian is identified. Long non‑coding (lnc)RNAs were determined to serve critical functions in a variety of distinct types of cancer, including ovarian cancer; however, there is limited knowledge regarding the differential expression levels of lncRNAs in cisplatin‑resistant and cisplatin‑sensitive ovarian cancer. Therefore, in the present study, the expression levels were determined for these cancer types. The lncRNA expression profile in cisplatin‑resistant ovarian cancer was analyzed and compared with the results for cisplatin‑sensitive ovarian cancer; gene ontology and pathway analysis demonstrated that the dysregulated lncRNAs participated in important biological processes. Subsequently, it was identified that these dysregulated lncRNAs were present in other ovarian cancer tissues and in SKOV3 ovarian cancer cells, as well as its cisplatin‑resistant clone, SKOV3/CDDP. In addition, it was revealed that 8 lncRNAs (Enst0000435726, Enst00000585612, Enst00000566734, Enst00000453783, NR_023915, RP11_697E22.2, uc010jub.1 and tcons_00008505) were associated with cisplatin‑resistant ovarian cancer. The present study may assist in improving understanding of the initiation and developmental mechanisms underlying cisplatin‑resistant ovarian cancer, which could aid future studies in discovering potential biomarkers for diagnosis or therapeutic targets that may be used in clinical treatment. [ABSTRACT FROM AUTHOR]

Abstract: With current diagnostic methods detection of stage 1 or 2 ovarian cancer using CA125 is possible in only 75% of cases. The ability to detect CA125 at lower concentrations could significantly improve such early stage diagnosis. Here, the use of screen‐printed graphene biosensors as a label‐free detection platform for CA125 was evaluated. The sensor was fabricated through deposition of a polyaniline layer via electropolymerisation on to a graphene screen‐printed electrode. The sensor surface was functionalised with anti‐CA125 antibody via covalent cross linking to polyaniline. The fabrication process was characterised through cyclic voltammetry and electrochemical impedance spectroscopy. The limit of detection achieved was 0.923 ng/μL across a dynamic range of 0.92 pg/μL–15.20 ng/μL and represents the most sensitive CA125 detection reported to date. With sensitivity limits at this level, it will now be possible to conduct clinical trials using serum samples collected from early stage ovarian cancer patients and at risk individuals. [ABSTRACT FROM AUTHOR]

Copyright of Ginecología y Obstetricia de México is the property of Federacion Mexicana de Ginecologia y Obstetricia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Multiple studies have shown that protein kinase Bβ (AKT2) is involved in the development and progression of ovarian cancer, however, its precise role remains unclear. Here we explored the underlying molecular mechanisms how AKT2 promotes ovarian cancer progression. We examined the effects of AKT2 in vitro in two ovarian cancer cell lines (SKOV3 and HEY), and in vivo by metastasis assay in nude mice. The migration and invasion ability of SKOV3 and HEY cells was determined by transwell assay. Overexpression and knockdown (with shRNA) experiments were carried out to unravel the underlying signaling mechanisms induced by AKT2. Overexpression of AKT2 led to increased expression of pyruvate kinase (PKM2) in ovarian cancer cells and in lung metastatic foci from nude mice. Elevated AKT2/PKM2 expression induced cell migration and invasion in vitro , as well as lung metastasis in vivo ; silencing AKT2 blocked these effects. Meanwhile, PKM2 overexpression was unable to increase AKT2 expression. The expressions of p-PI3K, p-AKT2, and PKM2 were increased when stimulated by epidermal growth factor (EGF); however, these expressions were blocked when inhibited the PI3K by LY294002. STAT3 expression was elevated and NF-κB p65 nuclear translocation was activated both in vitro and in vivo when either AKT2 or PKM2 was overexpressed; and these effects were inhibited when silencing AKT2 expression. Taken together, AKT2 increases the migration and invasion of ovarian cancer cells in vitro and promotes lung metastasis in nude mice in vivo through PKM2-mediated elevation of STAT3 expression and NF-κB activation. In conclusion, we highlight a novel mechanism of the AKT2-PKM2-STAT3/NF-κB axis in the regulation of ovarian cancer progression, and our work suggested that both AKT2 and PKM2 may be potential targets for the treatment of ovarian cancer. [ABSTRACT FROM AUTHOR]

There has been much progress in ovarian cancer screening and prevention in recent years. Improved tools that combine genetic and epidemiologic factors to predict an individual's ovarian cancer risk are set to become available for tailoring preventive and screening approaches. The increasing evidence on tubal origins of a proportion of ovarian cancer has paved the way to use of opportunistic bilateral salpingectomy at tubal ligation and hysterectomy in the general population. Clinical trials are in progress to estimate the long-term effects on endocrine function. In women at high risk, risk reducing salpingo-oophorectomy remains the standard of care with the current focus on management of resulting noncancer outcomes, especially sexual dysfunction in younger women. This has led to evaluation of early bilateral salpingectomy and delayed oophorectomy in this population. Meanwhile, modeling suggests that BRCA mutation carriers should consider using the oral contraceptive pill for chemoprevention. In the general population, the largest ovarian cancer screening trial to date, the UK Collaborative Trial of Ovarian Cancer Screening reported a stage shift with annual multimodal screening using the longitudinal CA 125 Risk of Ovarian Cancer Algorithm but not with annual transvaginal ultrasound screening. There was no definitive mortality reduction with either screening strategy compared with no screening. Further follow-up until December 2018 in now underway. Stage shift and higher rates of optimal cytoreduction were also reported during 3- to 4-monthly multimodal screening in the United Kingdom and U.S. high-risk screening trials. Although all agree that there is not yet evidence to support general population screening, recommendations for high-risk screening vary between countries. A key finding from the screening trials has been the better performance of longitudinal algorithms compared with a single cutoff for CA 125. A major focus of ovarian cancer biomarker discovery work has been tumor DNA markers in both plasma and novel specimens such as cervical cytology samples. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to assess the ability of a Next Generation Sequencing (NGS)-based approach in the detection of BRCA1/2 Large Genomic Rearrangements (LGRs). Methods We investigated 287 consecutive unrelated Italian women affected by breast or ovarian cancer. A NGS pipeline with a reliable Copy number Variation (CNV) prediction algorithm was applied. In addition, all samples were investigated using MAQ (Multiplex Amplicon Quantification) assay, while the MLPA (Multiplex Ligation-dependent Probe Amplification) technique was used as alternative method if necessary. Results Small pathogenic variants were identified in 80 samples. During NGS analysis, 11 samples were identified by Amplicon Suite Software (SmartSeq, Novara, Italy) as positive for large deletions or duplications. However, MAQ assay provided positive results in 19 patients. In particular, BRCA2 exon 25 deletion, not revealed by NGS CNV prediction algorithm, was detected in 8 unrelated women as false positive result. Sequencing analysis showed IVS24-113T/G (c.9257-113T>G) variant in 6 of these 8 patients, while the novel IVS24-129G>A (c.9257-129G>A) variant was detected in only two samples. Discussion The prevalence of large rearrangements in BRCA1/2 genes was the 12% of all disease-causing mutations detected in our patients. In particular, BRCA1 rearrangements were the 14.5% of all BRCA1 causing variants identified. Differently, BRCA2 large deletions were only the 6.9% of all mutations occurring in this gene. While MAQ assay showed 2,8% of false positive results, our integrative NGS-based approach fully satisfied the sensitivity and specificity parameters required on the BRCA1/2 LGRs detection. The workflow represents a robust and easy-to-use method for full BRCA1/2 screening, which can be easily implemented in routine diagnostic testing. [ABSTRACT FROM AUTHOR]

Objective: The aim of the current study was to explore barriers to genetic counseling and testing in women with gynecological cancers deemed at significant risk of carrying a germline mutation.Methods: A qualitative study using semi-structured interviews and inductively analysed thematically. Eight patients with ovarian or endometrial cancer participated in individual semi-structured telephone interviews that assessed motivation for genetic counseling and testing, perceived benefits and barriers, timing of the approach, perceptions of the referral process to genetic services and locus of control in relation to cancer and health.Results: Analysis of the interview transcripts revealed five themes relating to perceptions of genetic counseling and testing: Lack of importance; Level of information received; Timing of referral processes; Fear and anxiety; Resistance to and perceptions of counseling.Conclusions: Participants had a limited understanding of hereditary cancer syndromes and did not appreciate the benefits of genetic testing. A consistent approach at the time of referral to genetic services is needed to ensure that the level and format of information is appropriate for patients.Practice Implications: The rationale for genetic testing needs to be better explained to patients and the timing of referral should be based both on treatment priorities and patient preferences. [ABSTRACT FROM AUTHOR]

Evidence indicates that high-grade serous ovarian carcinoma arises from the fallopian tube, rather than ovarian surface epithelium. This is termed the 'tubal origin' theory. The aim of the present study was to compare the immunophenotype and gene expression profiling among high-grade serous ovarian carcinoma (HGSOC), fallopian tube epithelium (FTE) and ovarian surface epithelium (OSE) based on tubal origin theory, and identify the differential genes associated with ovarian carcinogenesis. A total of 61 cases of fresh tissue samples including 21 cases of HGSOC, 20 cases of OSE, and 20 cases of FTE were obtained following surgical resection. Immunostaining was performed to detect the expression of PAX8, which has been considered as a potential immunophenotype marker of Müllerian origin. Illumina BeadChip was applied for gene expression profiling. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to confirm the differential expression of candidate genes between HGSOC and FTE. The results of the present study demonstrated that PAX8 was highly expressed in HGSOC (19/21, 90.4%) and FTE (20/20, 100%), but not in OSE (3/20, 14.3%). A dendrogram generated by cluster analysis indicated a higher similarity of gene expression profile between HGSOC and FTE than OSE. A total of 2,412 differentially expressed genes were identified (absolute fold change >2) between HGSOC and FTE, including 822 upregulated genes in cancer and 1,590 downregulated genes. S100 calcium binding protein P, Ras-interacting protein 1, Wnt family member 5A, tumor-associated calcium signal transducer 2, Dickkopf Wnt signaling pathway inhibitor 3 and tumor suppressor candidate 3 genes were identified as candidate markers, of which the differential gene expression in HGSOC and FTE was confirmed by RT-qPCR (P<0.05). The results indicate the presence of a greater similarity in the immunophenotype and gene expression profile of HGSOC and FTE, when compared with OSE, which was consistent with the tubal origin theory of HGSOC. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the leading cause of female gynecological cancer mortality. Most patients with ovarian cancer are diagnosed with advanced stage because of lack of early symptoms, physical signs, and sensitive tumor biomarkers. The standard treatment includes cytoreductive surgery and platinum-based chemotherapy (usually platinum combined with paclitaxel). Despite that postoperative adjuvant chemotherapy prolongs survival time, most patients go through relapse within 6–12 months after the treatment. Thus, elucidating the molecular mechanism in cancer development is essential to promote early diagnosis and novel treatments. The role of exosome has been highlighted in multiple research fields in recent years. Exosome has been described as nano-sized vesicle secreted by multiple mammalian cell types, carrying cargos like proteins, miRNAs, mRNAs, and lipids. It participates in the formation of tumor microenvironment and the development of tumorigenesis and drug resistance in ovarian cancer. Meanwhile, it may also play a pivotal role in diagnosis, efficacy evaluation, and prognosis. Besides, studies show that exosome and its processed products have promising value in ovarian cancer treatment. The aim of the current review is to describe the characteristics of exosome in ovarian cancer, especially focusing on its role in immune modulation and drug resistance, hoping to provide new information on its implications in cancer diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Copyright of Ginecología y Obstetricia de México is the property of Federacion Mexicana de Ginecologia y Obstetricia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To exalore the clinical value of serum mesothelin conbined with CDK6 in the diagnosis of early ovarian cancer. Metiiods: 51 cases of patients who were diagnosed as stage I ~ II ovarian cancer (experimental group) in the department of obstetrics and gynecology of our hospital from June 2014 to June 2017 and 43 cases of patients with normal ovarian tissue were diagnosed by pathology(control group) and selected as the research object. The serum MSLN, CA125, CA199, HE4, VEGF-C levels and CDK6 expression of ovarian tissue were detected and compared. The significantly different indicators between the two groups were further analyzed by multifactor logistic regression. At the same time, the correlative analysis between the new index and the serum CA125, CA199 levels were carried out, the diagnostic value for early ovarian cancer was analyzed by ROC curve. Results: The serum MSLN, CA125, CA199, HE4, VEGF-C levels and CDK6 expression of experimental group were significantly higher in the experimental group than those of the control group (P<0.05). Multifactor logistic regression showed that serum MSLN, CA125 levels and CDK6 expression were valuable in the diagnosis of early ovarian cancer (P<0.05), and the serum CA125 had the highest impact(RR=1.421). The serum MSLN level of ovarian cancer patients(r=0.573, P=0.013) and the CDK6 expression of the Ovarian tissue (r=0.412 ,P=0.037) were positively correlated with serum CA125 level. ROC curves indicated that the area of the ROC curve of serum MSLN, CDK6 expression, serum CA125 and MSLN combined with CDK6 were 0.639, 0.700, 0.715 and 0.765, The area under the curve of MSLN combined with CDK6 was the highest. Conclusion: The clinical value of serum MSLN combined with CDK6 expression in the ovarian cancer tissue for the diagnosis of early ovarian cancer was superior to the conventional serological index CA125, CA199. [ABSTRACT FROM AUTHOR]

Background and Aim: To investigate the value of peripheral blood plasma levels of septin-9 and clusterin protein in the diagnosis of epithelial ovarian cancer (EOC).Materials and Methods: The peripheral blood plasma samples were obtained from 137 EOC patients, 12 borderline ovarian tumor patients, 10 benign ovarian tumor patients, 41 benign pelvic lesion patients, and 58 healthy women. The peripheral plasma septin-9 and clusterin proteins levels were measured by enzyme-linked immunosorbent assay. The power of test was evaluated with the area under the receiver operating characteristic curve (ROC) (AUC).Results: The mean levels of plasma septin-9 and clusterin in EOC patients were significantly higher than that in healthy women (P = 0.002, P = 0.021). The mean levels of plasma septin-9 in benign pelvic lesion patients were significantly higher than that in healthy women (P = 0.007). The mean levels of plasma septin-9 in epithelial ovarian carcinoma patients with tumor family history or distant metastases were significantly higher than that of patients without (P = 0.040, P = 0.025). The AUC of septin-9 protein was 0.712, when the optimal cut-off point was 0.28, the sensitivity and diagnostic specificity were 82.5% and 50.0%, respectively; the AUC of clusterin was 0.636, and when the optimal cut-off point was 87.96 ng/ml, the sensitivity and diagnostic specificity was 71.5% and 41.4%, respectively.Conclusion: The plasma levels of septin-9 and clusterin in ovarian cancer patients were abnormally elevated, which might be used as potential candidates of peripheral blood tumor biomarkers for early diagnosis of EOC and septin-9 might be related to distal metastases of EOC. The septin-9 might play the promotion role, which protein level relates to not only the distal metastases but also the prognosis of EOC. Due to the limit of sample volume, further enlargement of the sample size and set up of the follow-up system is in need to in-depth study the relationship between plasma protein concentration with the distal metastases, and further explore its correlation with the prognosis of EOC. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to investigate the clinical value of serum B7 homologous body 4 (B7-H4) protein detection for the diagnosis of ovarian cancer (OC) in Chinese Han women by pooling published data.Methods: A systematic literature search was conducted in Cochrane Library, PubMed, EMBASE, Wanfang, and China National Knowledge Infrastructure databases. The bivariate model was utilized to calculate the pooled estimates. Publication bias was assessed by using funnel plots and Deek's test.Results: After the review, ten publications were found to meet our inclusion criteria. The overall diagnostic sensitivity and specificity of B7-H4 in OC were 0.782 (95% confidence interval [CI]: 0.732-0.825) and 0.870 (95% CI: 0.804-0.916), respectively. The area under summary receiver operating characteristic curves was 0.86 (95% CI: 0.83-0.89). No significant publication bias was observed in the included studies.Conclusion: Serum B7-H4 detection, either alone or in combination with carbohydrate antigen 125, has an acceptable value in the diagnosis of OC. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study is to review all peer-reviewed published reports of women receiving ovarian tissue transplantation (OTT) with frozen/thawed tissue (OTC) with respect to age, diagnosis, transplantation site, fertility outcome, and potential side effects, including data from all women in the Danish program.Methods: A systematic review of the literature was performed in PubMed combined with results from all patients who had received OTT in Denmark up to December 2017.Results: OTT has been reported from 21 different countries comprising a total of 360 OTT procedures in 318 women. In nine women, malignancy was diagnosed after OTT; none were considered to be directly caused by the OTT. Despite a potential under reporting of cancer recurrence, there is currently no evidence to suggest that OTT causes reseeding of the original cancer. Renewed ovarian endocrine function was reported in 95% of the women. Half of all children born following OTT resulted from natural conception, and newborns were reported to be healthy except for one neonate with a chromosome anomaly with a family disposition. Women who conceived after OTT were significantly younger than those who failed.Conclusion: This study found no indications of sufficient numbers of malignant cells present in the ovarian tissue to cause recurrence of cancer after OTT. Further, it is unlikely that OTC affects the well-being of children born. OTC is now an established method of fertility preservation in Denmark with public reimbursement. The current data encourage that women who require gonadotoxic treatment should be offered an individual evaluation considering fertility preservation. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the available randomized controlled trials (RCTs) in the literature investigating the use of gonadotropin-releasing hormone agonist (GnRHa) co-treatment for ovarian preservation in women receiving chemotherapy.Methods: A systematic review of the literature was performed from 1960 through 2017 to identify relevant RCTs. Included patients had lymphoma, ovarian cancer, or breast cancer. The primary outcome was the proportion of women who retained ovarian function after chemotherapy. Extracted data points included study design, patient characteristics, and proportion of women who developed premature ovarian failure (POF). A risk of bias assessment was performed according to the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. The pooled odds ratio was calculated, and outcomes of individual studies were compared using the random-effects model with the inverse-variance method and the DerSimonian-Laird estimator.Results: Twenty-nine RCTs were identified, and 10 met criteria for inclusion in the meta-analysis. An analysis of patients who did not develop POF after chemotherapy revealed eight studies supporting the use of GnRHa (OR 1.83; 95% CI 1.34-2.49). The duration of benefit of GnRHa is unclear. An analysis of three studies with outcome data at 2 years revealed a non-significant OR of 0.53 (95% CI 0.22-1.30) for the preservation of ovarian function with GnRHa treatment.Conclusion: GnRHa may have a protective effect against the development of POF after gonadotoxic chemotherapy; however, the duration of benefit is unclear and requires further study. [ABSTRACT FROM AUTHOR]

Objective High grade serous ovarian cancer (HGSC) remains one of the most lethal malignancies in females. We previously reported that γ-glutamyl cyclotransferase (GGCT) was significantly upregulated in serous ovarian cancer. The current study was aimed to explore the function and underlying mechanism of GGCT in HGSC. Methods GGCT expression was assessed by immunohistochemistry in 128 HGSC patients. Stable cell lines with GGCT gene overexpression or knockdown were established to investigate the function of GGCT in HGSC in vitro and in vivo . Results GGCT is highly upregulated in HGSC tissues and associated with FIGO stage, lymph node metastasis and ascitic fluid volume. High expression of GGCT is associated with poor survival in HGSC patients. The Harrell's c-indexes of the prognostic models for overall survival and progression-free survival prediction were 0.758 and 0.726, respectively. GGCT knockdown suppresses proliferation, clone formation, migration, and invasion of tumor cells in vitro while forced GGCT overexpression presents opposite results. Furthermore, GGCT silencing inhibits tumor growth and spread in vivo . Epithelial-mesenchymal transition (EMT) and PI3K/AKT/mTOR signaling pathway are suppressed in GGCT silenced cells and enhanced in GGCT overexpressed cells. Inactivation of PI3K/AKT/mTOR signaling pathway in GGCT overexpressed cells induces EMT inhibition. Conclusions Our data reveals an important role of GGCT in regulating EMT and progression of HGSC, providing a valuable prognostic marker and potential target for treatment of HGSC patients. [ABSTRACT FROM AUTHOR]

Objectives To measure the effectiveness of ovarian cancer screening using the Risk of Ovarian Cancer Algorithm (ROCA). Methods A Markov model was constructed based on the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). This model was used to predict the outcome of ovarian cancer screening with ROCA. Results The model predicted the ovarian cancer mortality from age 50 to age 85 to be 0.954% with a decrease in life expectancy of 0.178 years (yrs) per person. Using data from the UKCTOCS the model predicted a similar reduction in mortality (11% vs. 10%), and similar curves for ovarian cancer mortality. Screening at age 50 for 20 yrs reduced ovarian cancer mortality from 0.953% to 0.898%, an absolute decrease of 6%, yielding an increase in life expectancy of 0.0101 yrs, preventing 55 deaths per 100,000 screened at a cost of $585,946 per life-yr. Screening for 30 yrs reduced mortality from 0.954% to 0.872%, an absolute decrease of 9%, preventing 82 deaths at a cost of $763,970 per life-yr. Conclusion The ROCA test can improve the detection of early ovarian cancer but is not practical for screening in an average-risk population. We predict the ROCA test will reduce overall ovarian cancer mortality by 6% to 9% but at a substantial cost. For ROCA to be practical, the cost would need to be reduced ten-fold and would have only a marginal impact on mortality from ovarian cancer. This model supports the FDA's criticism of the ROCA test. Ovarian cancer screening may reduce mortality from ovarian cancer but is not cost effective. [ABSTRACT FROM AUTHOR]

Objective: The current rearrangement ratio of BRCA1 and BRCA2 genes is not known in the Turkish population. Rearrangements are not routinely investigated in many Turkish laboratories. This creates problems and contradictions between clinics. Therefore, the aim of this study was to evaluate the distribution and frequency of rearrangements in BRCA1 and BRCA2 genes in high-risk families and to clarify the limits of BRCA1 and BRCA2 testing in Turkey. Materials and Methods: The study included 1809 patients at high risk of breast cancer or ovarian cancer. All patients were investigated for both small indels and rearrangements of BRCA genes using DNA sequencing and multiplex ligation-dependent probe amplification (MLPA) analysis. Results: The overall frequency of rearrangements was 2% (25/1262). The frequency of rearrangements was 1.7% (18/1086) and 4% (9/206) in patients with breast cancer and ovarian cancer, respectively. The frequency of rearrangements was 3.7% (8/215) in patients with triple-negative breast cancer. The rearrangement rate was 7.7% (2/26) in patients with both breast and ovarian cancer. Conclusions: Rearrangements were found with high rates and were strongly associated with bilateral and triple-negative status of patients with breast cancer, which are signs of high risk for breast and ovarian cancer. Analysis of rearrangements should definitely be included in routine clinical practice in Turkey for high-risk families and also for improved cancer risk prediction for families. [ABSTRACT FROM AUTHOR]

The article focuses on a study regarding the engineering of prototype optical sensor composed of an antibody-functionalized carbon nanotube complex for the detection of high-grade serous ovarian carcinoma (HGSC) biomarker. Topics discussed include U.S. Food and Drug Administration (FDA) has approved cancer antigen 125 and human epididymis protein 4 (HE4) as biomarker for HGSC, response of HE4 via modulation of the nanotube optical bandgap and progress in electronic implants.

Ovarian cancer is one of the prime causes of mortality in women. Diagnosis of ovarian cancer using ultrasonography is tedious as ovarian tumors exhibit minute clinical and structural differences between the suspicious and non-suspicious classes. Early prediction of ovarian cancer will reduce its growth rate and may save many lives. Computer-aided diagnosis (CAD) is a noninvasive method for finding ovarian cancer in its early stage which can avoid patient anxiety and unnecessary biopsy. This study investigates the efficacy of a novel CAD tool to characterize suspicious ovarian cancer using Radon-transformed nonlinear features. The obtained dimension of the extracted features is reduced using Relief-F feature selection method. In this study, we have employed the fuzzy forest-based ensemble classifier in contrast to the known crisp rule-based classifiers. The proposed method is evaluated using 469 (non-suspicious: 238, suspicious: 231) subjects and achieved a maximum 80.60 ± 0.5% accuracy, 81.40% sensitivity, 76.30% specificity with fuzzy forest, an ensemble fuzzy classifier using thirty-nine features. The proposed method is robust and reproducible as it uses maximum number subjects (469) as compared to state-of-the-art techniques. Hence, it can be used as an assisting tool by gynecologists during their routine screening. [ABSTRACT FROM AUTHOR]

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