Benign Pelvic Masses Research Articles

The diagnostic performance of the Mindray system in detecting CA125 and HE4 for patients with ovarian cancer.

Cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) are the most commonly used tumor biomarkers for ovarian cancer (OC) screening and diagnosis. The risk of ovarian malignancy algorithm (ROMA) score uses these markers, as detected by the Roche system, to predict the risk of OC. This study sought to assess the performance of the Mindray system in detecting CA125 and HE4 for ROMA score calculation in clinical settings. Consecutive OC patients and patients with benign pelvic masses were screened and enrolled in this study. The CA125 and HE4 levels of these patients were measured using both the Mindray and Roche systems. The ROMA score for each patient was calculated. Diagnostic performance was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. The HE4 and CA125 levels were significantly higher in the patients with OC than the patients with benign ovarian masses. Both detection systems showed high efficiency in detecting ovarian cancer. For the premenopausal OC patients, the AUC values for the ROMA score, HE4, and CA125 were 0.866, 0.852, and 0.879, respectively, using the Roche system, and 0.911, 0.902, and 0.883, respectively, using the Mindray system. For the postmenopausal OC patients, the AUC values for the ROMA score, HE4, and CA125 were 0.962, 0.920, and 0.953, respectively, using Roche system, and 0.966, 0.924, and 0.959, respectively, using the Mindray system. The correlation analysis showed strong agreement between the two systems. Among the patients who experienced recurrence, we observed a significant increase in both HE4 and CA125 levels compared to baseline using the Mindray system. The Mindray and Roche systems provide consistent results. The Mindray system can be used to detect HE4 and CA125 for ROMA score calculation.

Novel liquid biopsy assay to distinguish benign from malignant pelvic masses.

e17563 Background: Despite not ranking among the top ten most common cancers in women in the United States, ovarian cancer stands as the fifth leading cause of cancer-related deaths in this population. According to the American Cancer Society, only 20% of ovarian cancers are found at stages I-II, when 94% of patients are expected to live longer than five years after diagnosis. Instead, the majority of ovarian cancers are detected at stages III-IV, when long term survival is 20% or less. Early identification of ovarian cancer is challenging due to the wide range of symptoms with which a patient may present, most of which lack specificity for ovarian cancer. Even in cases where a physician may want to rule in or out ovarian cancer, the available methods for screening have a low positive predictive value. These methods include bimanual exams, transvaginal ultrasounds, and CA-125 blood tests. In a screening capacity, the sensitivity for a bimanual exam finding ovarian cancer is only about 44%, transvaginal ultrasound is approximately 85%, and CA-125 testing registers at 77%. The need for better tools to detect ovarian cancer is clear. Genece Health has developed an assay utilizing a proprietary algorithm that leverages deep learning to analyze cfDNA fragment size, end motif, and coverage patterns, along with other genomic features, to detect the presence of ctDNA in blood originating from ovarian cancer. The data presented herein demonstrate that the Genece Health assay has the ability to detect ctDNA in a single tube of blood using low pass whole genome sequencing in a cost-effective way to distinguish between malignant and benign pelvic masses. Methods: Blood was prospectively collected from 56 females with pelvic masses in advance of removal and histopathology (approximately 32 cancer and 24 benign masses) in Streck cfDNA BCT Devices. Additionally, healthy female donor blood from 50 individuals procured through the San Diego Blood Bank were collected in Streck cfDNA BCT Devices. cfDNA was extracted from double-spun plasma and low-pass whole genome sequencing (2X – 5X coverage) was performed. Data were analyzed with the Genece Health Algorithm. Results: The Genece Health Algorithm demonstrated the ability to distinguish between pelvic masses that were deemed benign versus malignant via histopathology. There was a significant (P<0.01) difference between the classifier assigned to the malignant and benign and presumed normal groups. Conclusions: The investigational assay described herein shows progress toward the ability to use non-invasive molecular testing to identify ovarian cancer in a blood sample. A blood test to differentiate between a benign and malignant pelvic mass will enhance the ability of physicians to detect ovarian cancer at earlier stage, improving clinical outcomes for women. The cost-effective low-pass whole genome sequencing approach taken by Genece will be further explored in expanded cohorts.

Diagnosing and staging epithelial ovarian cancer by serum glycoproteomic profiling.

There is a need for diagnostic tests for screening, triaging and staging of epithelial ovarian cancer (EOC). Glycoproteomics of blood samples has shown promise for biomarker discovery. We applied glycoproteomics to serum of people with EOC or benign pelvic masses and healthy controls. A total of 653 analytes were quantified and assessed in multivariable models, which were tested in an independent cohort. Additionally, we analyzed glycosylation patterns in serum markers and in tissues. We identified a biomarker panel that distinguished benign lesions from EOC with sensitivity and specificity of 83.5% and 90.1% in the training set, and of 86.7 and 86.7% in the test set, respectively. ROC analysis demonstrated strong performance across a range of cutoffs. Fucosylated multi-antennary glycopeptide markers were higher in late-stage than in early-stage EOC. A comparable pattern was found in late-stage EOC tissues. Blood glycopeptide biomarkers have the potential to distinguish benign from malignant pelvic masses, and early- from late-stage EOC. Glycosylation of circulating and tumor tissue proteins may be related. This study supports the hypothesis that blood glycoproteomic profiling can be used for EOC diagnosis and staging and it warrants further clinical evaluation.

Autoantibodies, antigen-autoantibody complexes and antigens complement CA125 for early detection of ovarian cancer

BackgroundMultiple antigens, autoantibodies (AAb), and antigen-autoantibody (Ag-AAb) complexes were compared for their ability to complement CA125 for early detection of ovarian cancer.MethodsTwenty six biomarkers were measured in a single panel of sera from women with early stage (I-II) ovarian cancers (n = 64), late stage (III-IV) ovarian cancers (186), benign pelvic masses (200) and from healthy controls (502), and then split randomly (50:50) into a training set to identify the most promising classifier and a validation set to compare its performance to CA125 alone.ResultsEight biomarkers detected ≥ 8% of early stage cases at 98% specificity. A four-biomarker panel including CA125, HE4, HE4 Ag-AAb and osteopontin detected 75% of early stage cancers in the validation set from among healthy controls compared to 62% with CA125 alone (p = 0.003) at 98% specificity. The same panel increased sensitivity for distinguishing early-stage ovarian cancers from benign pelvic masses by 25% (p = 0.0004) at 95% specificity. From 21 autoantibody candidates, 3 AAb (anti-p53, anti-CTAG1 and annt-Il-8) detected 22% of early stage ovarian cancers, potentially lengthening lead time prior to diagnosis.ConclusionA four biomarker panel achieved greater sensitivity at the same specificity for early detection of ovarian cancer than CA125 alone.

Surgical management of uterine fibroids.

Fibroids are benign pelvic masses and constitute the most common gynaecological condition. They create a significant health and social burden to many women because of heavy menstrual bleeding and fibroid pressure symptoms. Many women will be faced with the dilemma of surgical management to improve their symptoms at some point of their reproductive age. The aim of this article is to identify current surgical management of fibroids describing the technical steps, advantages, disadvantages and risks of each method. The surgical management of fibroids remains challenging, as the overall prevalence, the clinical experience and the patient awareness is increasing because of an upgrade in our sonographic and magnetic resonance diagnostic tools. Unfortunately not every patient is able to benefit from tailor-made surgery that holistically evaluates individual needs including fertility aspirations. This article provides the most current synopsis of every available surgical modality for fibroid management. Large prospective multicentre cohort studies are needed to definitely determine the most suitable operation for any individual suffering with fibroids; and perhaps artificial intelligence may offer a valuable tool in the future data analysis.

Contribution of Outpatient Ultrasound Transvaginal Biopsy and Puncture in the Diagnosis and Treatment of Pelvic Lesions: A Bicenter Study.

The use of transvaginal ultrasound guided biopsy and puncture of pelvic lesions is a minimally invasive technique that allows for accurate diagnosis. It has many advantages compared to other more invasive (lower complication rate) or non-invasive techniques (accurate diagnosis). Furthermore, it offers greater availability, it does not radiate, enables the study of pelvic masses accessible vaginally with ultrasound control in real time, and it is possible to use the colour Doppler avoiding puncturing large vessels among others. The main aim of the work is to describe a standardized ambulatory technique and to determine its usefulness. This is a retrospective study of ultrasound transvaginal punctures (core needle biopsies and cytologies) and drainages of pelvic lesions performed on an outpatient basis during the last two years. The punctures were made with local anesthesia, under transvaginal ultrasound guidance with an automatic or semi-automatic 18G biopsy needle with a length of 20-25 cm and a penetration depth of 12 or 22 mm. The material obtained was sent for anatomopathological, cytological and/or microbiological study if necessary. A total of 42 women were recruited in two centers. Fifty procedures (nine punctures, seven drains, and 34 biopsies) were performed. In five cases the punction and drain provided clinical relief in benign pelvic masses. Regarding material of the biopsies performed, 15 were vaginal in women previously histerectomized, finding 10 carcinomas, eight were ovarian tumours in advanced stages or peritoneal carcinomatosis obtaining the appropriate histology in each case, seven were suspicious cervical biopsies finding carcinomas in five of them, three were myometrial biopsies including one breast carcinoma metastasis in the miometrium and a benign placental nodule, and a periurethral biopsy was performed on a woman with a history of endometrial cancer confirming recurrence. The pathological diagnosis was satisfactory in all cases, confirming the nature of the lesion (25 malignant-ten vaginal recurrences of previous gynaecological cancers, eight cases of primary ovarian/peritoneal carcinoma, four new diagnosis of cervical malignant masses, one cervical metastasis of lymphoma, one periurethral recurrence of endometrial carcinoma and one recurrence of breast cancer in the myometrium-and 23 benign). The tolerance was excellent and no complications were detected. The ambulatory ultrasound transvaginal puncture and drainage technique is useful for obtaining a sample for pathological and microbiological diagnosis with excellent tolerance that can be used to rule out the recurrence of malignant lesions or progression of the disease, diagnose masses not accessible to gynecological exploration (vaginal vault, myometrium or cervix) and for early histologic diagnosis in cases of advanced peritoneal carcinomatosis or ovarian carcinoma as well as drainage and cytological study of cystic pelvic masses.

A Blood-Based Metabolite Panel for Distinguishing Ovarian Cancer from Benign Pelvic Masses.

To assess the contributions of circulating metabolites for improving upon the performance of the risk of ovarian malignancy algorithm (ROMA) for risk prediction of ovarian cancer among women with ovarian cysts. Metabolomic profiling was performed on an initial set of sera from 101 serous and nonserous ovarian cancer cases and 134 individuals with benign pelvic masses (BPM). Using a deep learning model, a panel consisting of seven cancer-related metabolites [diacetylspermine, diacetylspermidine, N-(3-acetamidopropyl)pyrrolidin-2-one, N-acetylneuraminate, N-acetyl-mannosamine, N-acetyl-lactosamine, and hydroxyisobutyric acid] was developed for distinguishing early-stage ovarian cancer from BPM. The performance of the metabolite panel was evaluated in an independent set of sera from 118 ovarian cancer cases and 56 subjects with BPM. The contributions of the panel for improving upon the performance of ROMA were further assessed. A 7-marker metabolite panel (7MetP) developed in the training set yielded an AUC of 0.86 [95% confidence interval (CI): 0.76-0.95] for early-stage ovarian cancer in the independent test set. The 7MetP+ROMA model had an AUC of 0.93 (95% CI: 0.84-0.98) for early-stage ovarian cancer in the test set, which was improved compared with ROMA alone [0.91 (95% CI: 0.84-0.98); likelihood ratio test P: 0.03]. In the entire specimen set, the combined 7MetP+ROMA model yielded a higher positive predictive value (0.68 vs. 0.52; one-sided P < 0.001) with improved specificity (0.89 vs. 0.78; one-sided P < 0.001) for early-stage ovarian cancer compared with ROMA alone. A blood-based metabolite panel was developed that demonstrates independent predictive ability and complements ROMA for distinguishing early-stage ovarian cancer from benign disease to better inform clinical decision making.

Somatic single nucleotide variations and copy number variation can be used to distinguish high grade serous ovarian cancer from benign fallopian tubes with high accuracy (219)

Somatic single nucleotide variations and copy number variation can be used to distinguish high grade serous ovarian cancer from benign fallopian tubes with high accuracy (219)

THE COMPARATIVE STUDY OF USG AND MDCT IN THE EVALUATION OF PELVIC MASSES IN FEMALES

Introduction: Pelvic masses in females of all ages are a routine gynaecological issue for which healthcare is sought, and in a populous country like India, these masses form a significant part of the disease burden. The evaluation of the female pelvis is a radiological necessity and a challenge. The foremost aim for any imaging modality in this scenario is to rule out malignancy in the mass, and further to characterise and define the mass so as to guide appropriate management of the patient. Of the wide range of imaging modalities available, ultrasonography and computed tomography are commonly available and extensively used for the evaluation of the varied female pelvic masses. We studied the ultrasonography and multi detector computed tomography findings and their usefulness in the diagnosis and characterization of various pelvic masses in females. Methodology: It was a prospective observational study, ranging over the duration of one and a half years,of 100 female patients fulfilling inclusion criteria, who underwent ultrasonography and multidetector computed tomography scanning in the Department of Radiodiagnosis at RNT medical college, Udaipur. Pelvic masses were evaluated for origin, size, margins, composition, vascularity, ascites, lymphadenopathy and other features to characterise as benign or malignant. Final diagnosis was by histopathological correlation. Results: The most common age group belonged to 35-45 years group (22%) followed by 55-65 years group (21%). Mean age for benign masses was 35.84 years and for malignant masses was 51.64 years. Ovarian origin was the commonest followed by uterine origin. Features like solid areas, ill-defined margins, lymphadenopathy and ascites favoured malignancy. Most common pathologies were adenocarcinoma ovary, carcinoma cervix, benign ovarian cysts and uterine fibroids. Conclusion: Ultrasonography is often the first imaging study performed in patients with symptoms related to the pelvis. Results indicated higher diagnostic capability of CT as a problem-solving tool. Overall diagnostic accuracy of CT was higher than USG in characterising both benign and malignant pelvic masses.

Detection of ovarian cancer using plasma cell-free DNA methylomes

BackgroundOvarian cancer (OC) is a highly lethal gynecologic cancer, and it is hard to diagnose at an early stage. Clinically, there are no ovarian cancer-specific markers for early detection. Here, we demonstrate the use of cell-free DNA (cfDNA) methylomes to detect ovarian cancer, especially the early-stage OC.Experimental designPlasma from 74 epithelial ovarian cancer patients, 86 healthy volunteers, and 20 patients with benign pelvic masses was collected. The cfDNA methylomes of these samples were generated by cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq). The differentially methylated regions (DMRs) were identified by the contrasts between tumor and non-tumor groups, and the discrimination performance was evaluated with the iterative training and testing method.ResultsThe DMRs identified for cfDNA methylomes can well discriminate tumor groups and non-tumor groups (ROC values from 0.86 to 0.98). The late-stage top 300 DMRs are more late-stage-specific and failed to detect early-stage OC. However, the early-stage markers have the potential to discriminate all-stage OCs from non-tumor samples.ConclusionsThis study demonstrates that cfDNA methylomes generated with cfMeDIP-seq could be used to identify OC-specific biomarkers for OC, especially early OC detection. To detect early-stage OC, the biomarkers should be directly identified from early OC plasma samples rather than mix-stage ones. Further exploration of DMRs from a k larger early-stage OC cohort is warranted.

Liquid-biopsy-derived glycoproteomic profiling as a novel means for noninvasive diagnosis of ovarian cancer.

e17604 Background: Ovarian cancer (OC) is the fifth- leading cause of cancer-related deaths among women, and the most lethal gynecological cancer. Currently available biomarkers, including CA-125 and HE4, show suboptimal diagnostic performance for differentiating among benign and malignant pelvic tumors, and the early recognition of OC. Differentiation of benign and malignant pelvic tumors is required for proper patient triaging and management, yet non-invasive methods remain a largely unmet medical need. Methods: We applied a novel platform for characterizing peripheral blood glycoproteomic biomarkers, combining liquid-chromatography/mass spectrometry (LC-MS) with artificial intelligence/neural networks (AI-NN) for the targeted quantification of serum protein glycosylation at intact glycopeptide level to analyze serum samples from 296 treatment-naïve women with histopathology-confirmed diagnosis of either benign (n = 151) or malignant (n = 145) tumors, and from 55 healthy control subjects, procured from a commercial biobank. Using data-dependent acquisition, a panel of 683 serum glycosylated and non-glycosylated peptides, representing 71 serum proteins, was interrogated. Samples were randomly divided into a training and a testing set for multivariable analysis. Data processing was performed using PB-Net, an in-house-developed high-throughput peak integration software. Raw data were normalized, processed by statistical analysis, and applied to machine learning models. Results: Comparison of glycopeptide abundances among patients with OC and benign pelvic tumors yielded 428 statistically significantly differentially expressed glycopeptides/peptides (at FDR &lt; 0.05). A subpanel of these markers used to generate a score for predicting OC yielded areas under the receiver-operating-characteristic of 0.955 and 0.894 in the training and testing sets, respectively. The predicted probability of malignancy increased with cancer stage, and probability distributions were similar across training and test sets. Applying the model to healthy subjects, not utilized in training, resulted in few misclassifications and a spread nearly equivalent to that of the benign tumor cases. This indicates the signature robustly predicts malignancy and severity of disease. Conclusions: Our novel approach exhibited impressive levels of accuracy for the noninvasive differentiation of benign and malignant pelvic masses, compared with existing biomarkers and algorithms, thereby demonstrating the utility of glycoprotein profiles as a powerful, noninvasive new diagnostic modality.

The diagnostic accuracy of human epididymis protein 4 (HE4) for discriminating between benign and malignant pelvic masses: a systematic review and meta-analysis.

Many women with benign pelvic masses, suspected of ovarian cancer, are unnecessarily referred for treatment at specialized centers. There is an unmet clinical need to improve diagnostic assessment in these patients. Our objective was to obtain summary estimates of the accuracy of human epididymis protein (HE4) for diagnosing ovarian cancer and to compare the performance of HE4 with that of cancer antigen 125 (CA125). We searched PubMed, Ovid and Scopus using search terms for "pelvic masses" and "HE4", to identify studies that evaluated HE4 for diagnosing malignant ovarian masses, in adult women presenting with a pelvic mass, suspected of ovarian cancer, and with diagnosis confirmed by histopathology. Screening, data extraction and Risk of Bias assessment with the QUADAS-2 tool were done independently by two authors. We performed a meta-analysis of the accuracy of HE4 and CA125 using a random-effects bivariate logit-normal model. A study protocol was registered at PROSPERO (CRD42020158073). In the 17 eligible studies, which included 3404 patients, ovarian cancer prevalence ranged from 15% to 71%. Overall, the studies were heterogeneous. All studies seemed to have recruited patients in specialized settings. A meta-analysis of seven HE4 studies resulted in a mean sensitivity of 79.4% (95% confidence interval [CI] 74.1%-83.8%) and a mean specificity of 84.1% (95% CI 79.6%-87.8%), for cut-off values of 67-72pmol/L. Based on eight studies, the mean sensitivity of CA125 was 81.4% (95% CI 74.6%-86.2%) and the mean specificity was 56.8% (95% CI 47.9%-65.4%), at a cut-off of 35U/ml. Given a 40% ovarian cancer prevalence, the positive predictive value (PPV) for HE4 would be 76.9% (71.9%-81.2%) vs 55.6% (50.2%-60.9%) for CA125. The negative predictive value (NPV) would be 85.9 (82.8%-88.6%) and 81.9% (76.2%-86.4%), respectively. At a 15% prevalence, the NPV would be 95.8% (95% CI 94.4%-96.7%) for HE4 and 94.4% (95% CI 92.3%-96.0%) for CA125. The PPV would be 46.9% (40.4%-53.4%) and 24.9% (21.1%-29.2%), respectively. HE4 had higher specificity and similar sensitivity compared with CA125. At high prevalence, PPV was also higher for HE4, but at low prevalence, it had a similar NPV to CA125. The field would benefit from studies conducted in general settings.

Complete resolution of a giant multilocular prostatic cystadenoma following androgen deprivation therapy: an illustrative case report

ABSTRACTGiant multilocular prostatic cystadenoma (GMPC) is a rare benign pelvic mass for which complete surgical resection is an accepted treatment of choice. This report presents the first case of complete resolution of GMPC following a 3-year course of luteinising hormone-releasing hormone agonist alongside external beam radiotherapy for the concurrent treatment of unfavorable intermediate-risk prostate cancer. In addition to illustrating the imaging features of the effect of androgen deprivation therapy (ADT) and radiotherapy on GMPC regression, this case provides evidence for considering ADT as an alternative, noninvasive GMPC treatment option in patients in whom surgical treatment is either contraindicated or can be made less invasive by reducing the size of GMPC prior to its removal.

English

BACKGROUND Ultrasonography (USG) is the diagnostic test of choice in evaluating pelvic masses. Because of considerable overlap in the morphologic pattern of different pelvic masses, diagnosis should be correlated with histopathological findings. We wanted to do an ultrasonographic evaluation of pelvic masses and study its correlation with histopathology in a teaching hospital. METHODS This is a prospective study done among 40 cases subjected to USG at Department of Radiology, Hyderabad, Telangana, over a period of seven months. The USG findings were noted and were correlated with the final histopathological findings. The sensitivity and specificity of ultrasound for malignancy were 75 % and 88.8 % respectively. RESULTS In the present study ovarian masses were most frequent (67.5 %), followed by uterine (25 %) and adnexal masses (7.5 %). Majority of the benign pelvic masses (67 %) were seen in the age group of 31 – 40 years while malignant pelvic masses (15 %) were more common in the age group of 51 – 60 years. CONCLUSIONS Ultrasonography is the first choice imaging technique to investigate pelvic masses in women. Of all gynaecological pelvic masses, ovarian masses are the commonest. Sonography has good sensitivity and specificity and is very effective in diagnosis of gynaecological masses and it correlates well with the final histopathological diagnosis. KEYWORDS Ultrasonography, Pelvic Masses, Ovarian Masses, Histopathology

A MYC-Driven Plasma Polyamine Signature for Early Detection of Ovarian Cancer.

Simple SummaryThere is a need for additional marker(s) to detect early-stage ovarian cancer that would augment the performance of CA125. Herein, we report a polyamine signature that is detected in the blood and that has value for detecting ovarian cancers at an early stage. The polyamine signature was able to complement CA125 in identifying more ovarian cancer cases that would have been missed by CA125 alone. Our validation of a polyamine signature provides compelling evidence for the value of blood polyamine metabolites as markers for ovarian cancer detection.MYC is an oncogenic driver in the pathogenesis of ovarian cancer. We previously demonstrated that MYC regulates polyamine metabolism in triple-negative breast cancer (TNBC) and that a plasma polyamine signature is associated with TNBC development and progression. We hypothesized that a similar plasma polyamine signature may associate with ovarian cancer (OvCa) development. Using mass spectrometry, four polyamines were quantified in plasma from 116 OvCa cases and 143 controls (71 healthy controls + 72 subjects with benign pelvic masses) (Test Set). Findings were validated in an independent plasma set from 61 early-stage OvCa cases and 71 healthy controls (Validation Set). Complementarity of polyamines with CA125 was also evaluated. Receiver operating characteristic area under the curve (AUC) of individual polyamines for distinguishing cases from healthy controls ranged from 0.74–0.88. A polyamine signature consisting of diacetylspermine + N-(3-acetamidopropyl)pyrrolidin-2-one in combination with CA125 developed in the Test Set yielded improvement in sensitivity at >99% specificity relative to CA125 alone (73.7% vs 62.2%; McNemar exact test 2-sided P: 0.019) in the validation set and captured 30.4% of cases that were missed with CA125 alone. Our findings reveal a MYC-driven plasma polyamine signature associated with OvCa that complemented CA125 in detecting early-stage ovarian cancer.

Circulating Cell-Free DNA Methylation Profiles in the Early Detection of Ovarian Cancer: A Scoping Review of the Literature.

Simple SummaryThere are limited non-invasive methods for detecting epithelial ovarian cancer despite early detection and treatment dramatically increasing survival. As alterations in serum or plasma cell-free (cf)DNA methylation occur early in cancer development, they are promising biomarkers for ovarian cancer. Our literature review includes 18 studies depicting a wide array of gene targets and techniques. The data suggest a good performance of these cfDNA methylation tests, with accuracies up to 91% in detecting ovarian cancer in serum or plasma.Epithelial ovarian cancer is the most lethal gynecologic malignancy and has few reliable non-invasive tests for early detection or diagnosis. Recent advances in genomic techniques have bolstered the utility of cell-free DNA (cfDNA) evaluation from peripheral blood as a viable cancer biomarker. For multiple reasons, comparing alterations in DNA methylation is particularly advantageous over other molecular assays. We performed a literature review for studies exploring cfDNA methylation in serum and plasma for the early diagnosis of ovarian cancer. The data suggest that serum/plasma cfDNA methylation tests have strong diagnostic accuracies for ovarian cancer (median 85%, range 40–91%). Moreover, there is improved diagnostic performance if multiple genes are used and if the assays are designed to compare detection of ovarian cancer with benign pelvic masses. We further highlight the vast array of possible gene targets and techniques, and a need to include more earlier-stage ovarian cancer samples in test development. Overall, we show the promise of cfDNA methylation analysis in the development of a viable diagnostic biomarker for ovarian cancer.

PERFORMANCE OF THE IOTA ADNEX MODEL IN PREOPERATIVE ASSESSMENT OF SUSPICIOUS ADNEXAL MASSES WITH HIGH- RISK OF MALIGNANCY INDEX IN ALEXANDRIA UNIVERSITY GYNECOLOGICAL ONCOLOGY CENTER

• Ovarian cancer is the leading cause of death among all gynecological malignancies.• Early detection of ovarian cancer is the key to successful treatment. In addition, the appropriate preoperative differentiation between ovarian cancer and benign pelvic masses could notably improve the survival rate and the prognosis of ovarian cancer.• The risk of malignancy index (RMI) is a simple scoring system to discriminate the ovarian tumors. RMI is the most utilized, widely available, and validated effective triaging system for women with suspected ovarian cancer. • Recently, the International Ovarian Tumor Analysis (IOTA-ADNEX) model is one of the most useful prognostic tools to discriminates well between benign and malignant tumors and offers fair to excellent discrimination between four types of ovarian malignancy. • In clinical practice, the easily use of IOTA-ADNEX has the potential to improve triage and management decisions and so reduce morbidity and mortality associated with adnexal pathology.

Diagnostic plasma miRNA-profiles for ovarian cancer in patients with pelvic mass.

BackgroundOvarian cancer is the fifth most common cancer in women worldwide. Moreover, there are no reliable minimal invasive tests to secure the diagnosis of malignant pelvic masses. Cell-free, circulating microRNAs have the potential as diagnostic biomarkers in cancer. Here, we performed and validated a miRNA panel with the potential to distinguish OC from benign pelvic masses.MethodsThe profile of plasma microRNA was determined with a panel of 46 candidates in a discovery group and a validation group, each consisting of 190 pre-surgery plasma samples from age-matched patients with malignant (n = 95) and benign pelvic mass (n = 95), by real time RT-qPCR.ResultsFour up-regulated (miR-200c-3p, miR-221-3p, miR-21-5p, and miR-484) and two down-regulated (miR-195-5p and miR-451a) microRNAs were discovered. From those, miR-200c-3p and miR-221-3p were further confirmed in a validation cohort. A combination of these 2 microRNAs together with CA-125 yielded an overall diagnostic accuracy of AUC = 0.96.ConclusionsWe showed consistent plasma microRNA profiles that provide independent diagnostic information of late stage OC.

Abstract 1375: Multiplex gene expression using the HyCEAD assay in CTCs isolated with the Parsortix™ system

Abstract Background: Discrimination between benign and malignant pelvic masses by gene expression profiling of circulating tumor cells (CTCs) may provide information to assist in treatment decisions and improve outcomes. CTCs can be isolated and harvested from blood based on cell size and deformability using the Parsortix™ system. Because the number of CTCs in the blood of pelvic mass patients suspected of having ovarian malignancies is likely very low, gene expression profiling of these CTCs requires a highly sensitive detection system that is tolerant of the presence of normal nucleated blood cells. Objective: To assess the suitability of the HyCEAD assay for gene expression profiling of cells in Parsortix harvests. HyCEAD (Hybrid Capture Enrichment Amplification and Detection) is a fast and simple method for the simultaneous analysis of 100 or more mRNA species captured from cell lysates. The products of the multiplex amplification with HyCEAD can be quantified by hybridization on a flow-through chip. Methods: Multiple HyCEAD primer/probe sets were designed for 125 relevant genes, and purified total RNA or lysates from Parsortix harvests were processed with the HyCEAD assay. Primer/probe sets were screened using total RNA from cell lines and ovarian cancer tissues. Genes with significant expression in white blood cells were culled from the gene set. A set of non-human poly-adenylated mRNA molecules (separately quantified using digital droplet PCR) were used as spike-in standards to assess absolute sensitivity. CaOV3 cells spiked into blood from normal healthy volunteers (NHVs) were used as a model system for sensitivity analyses. Results: Many genes were identified that yielded substantially greater signal intensities in harvests from HNV blood spiked with CaOV3 cells relative to the unspiked blood samples. The expression levels could be quantified over a signal intensity range of 2.5 log10 units. Small numbers of non-human standard molecules could be detected; stochastic detection failures were observed when five or fewer molecules of the standards were assayed (dropout level). CVs in repeatability experiments were typically less than 20% with numbers of standard molecules greater than the dropout level. CVs in repeatability measurements of human genes related to ovarian cancer in spiked Parsortix harvests averaged about 25%. CVs were greater between assays of Parsortix harvests of different HNVs, reflecting in part biological variability and variation of the number of cells actually spiked into the blood and the number of cells recovered in the individual harvests. Conclusion: The HyCEAD assay provides adequate sensitivity to simultaneously profile expression levels of more than 100 genes in small numbers of CTCs directly from the lysates of Parsortix harvests. Expression profiling is limited to genes expressed at much higher levels in CTCs than in normal nucleated blood cells. Citation Format: David F. Englert, Mariya Kolesnikova, Nishat Zaman, Arianna Hustler, Gabrielle Wishart, Daniel J. O'Shannessy. Multiplex gene expression using the HyCEAD assay in CTCs isolated with the Parsortix™ system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1375.

Effects of hysterectomy with simultaneous bilateral salpingectomy on the subsequent pelvic mass

ObjectivesTo analyze the clinicopathological characteristics of subsequent pelvic masses after hysterectomy for benign diseases, and to compare the masses following hysterectomy with or without simultaneous bilateral salpingectomy.MethodsThis study retrospectively analyzed patients undergone reoperation for pelvic mass subsequently to previous hysterectomy for benign disease from January 2012 to December 2016 in Peking Union Medical College Hospital.ResultsA total of 247 patients were enrolled in this study, of which 80.16% (n = 198) received simple hysterectomy, and 5.67% (n = 14) underwent hysterectomy with bilateral salpingectomy. The clinicopathological data of patients undergone simple hysterectomy or simultaneous bilateral salpingectomy was compared. In the former group, we found that 68.18% (n = 135) of the pelvic massed were benign, and the remaining 31.82% (n = 63) were malignant. In latter group, 57.10% (n = 8) were benign (8%) and 42.90% (n = 6) were malignant. Univariate analysis showed that the age of surgery for pelvic masses in patients undergoing hysterectomy with simultaneous bilateral salpingectomy was significantly younger than that in patients without salpingectomy (median, 44.5 vs 50 years, P < 0.0001), and the time interval between hysterectomy and onset of pelvic masses was also significantly shorter (median, 2 vs 5 years, P < 0.0001). And the probability of pelvic encapsulated effusion was significantly higher for the salpingectomy group. Multivariate analysis showed that there was no significant difference of the age of resection of pelvic mass, the time interval hysterectomy and pelvic mass onset, and the probability of pelvic encapsulated effusion between the two groups.ConclusionsThe results showed that the incidence of secondary benign pelvic masses may be reduced when hysterectomy was performed with simultaneous bilateral salpingectomy. However, there was no statistical difference in the clinical characteristics and pathological types of pelvic masses between patients received hysterectomy with or without salpingectomy.