Early Detection Of Ovarian Cancer Research Articles

Screening for ovarian cancer: is there still hope?

SummaryMainly diagnosed at advanced stage, ovarian cancer still remains the most lethal gynecological malignancy. Regarding screening and early detection, ovarian cancer poses particular challenges. To date, no screening test has been proven capable of leading to a mortality benefit. In this short review, we summarize and discuss the underlying literature on screening for ovarian cancer, focusing on average-risk, asymptomatic women as well as women at high risk. We also discuss the continuous advances and limits in liquid biopsies for early detection and screening of ovarian cancer.

Improved early detection of ovarian cancer using longitudinal multimarker models

BackgroundOvarian cancer has a poor survival rate due to late diagnosis and improved methods are needed for its early detection. Our primary objective was to identify and incorporate additional biomarkers into longitudinal models to improve on the performance of CA125 as a first-line screening test for ovarian cancer.MethodsThis case–control study nested within UKCTOCS used 490 serial serum samples from 49 women later diagnosed with ovarian cancer and 31 control women who were cancer-free. Proteomics-based biomarker discovery was carried out using pooled samples and selected candidates, including those from the literature, assayed in all serial samples. Multimarker longitudinal models were derived and tested against CA125 for early detection of ovarian cancer.ResultsThe best performing models, incorporating CA125, HE4, CHI3L1, PEBP4 and/or AGR2, provided 85.7% sensitivity at 95.4% specificity up to 1 year before diagnosis, significantly improving on CA125 alone. For Type II cases (mostly high-grade serous), models achieved 95.5% sensitivity at 95.4% specificity. Predictive values were elevated earlier than CA125, showing the potential of models to improve lead time.ConclusionsWe have identified candidate biomarkers and tested longitudinal multimarker models that significantly improve on CA125 for early detection of ovarian cancer. These models now warrant independent validation.

Molecular Biomarkers for Early Detection and Prevention of Ovarian Cancer-A Gateway for Good Prognosis: A Narrative Review.

Gynecological cancers are one of the most lethal and deadliest cancers in the world. In India, the prevalence of ovarian cancer accounts for 2.5% to 3%. Despite the availability of improved treatment option along with improved technology, the survival rate of ovarian cancer in the early-stage and the advanced stage is poor. Therefore, due to the heterogeneity of ovarian cancer, to detect it at an early stage and to prevent further mortality turns out to be a big challenge. Researchers are still in the process to identify any single biomarker with good sensitivity and specificity. Various traditional and serum approaches to identify ovarian cancer have been successful in the early stages. The invention of molecular biomarkers such as the use of genomic profiling, DNA methylation, and other approaches have proven to be of higher sensitivity and specificity, which overall affects the prognosis of ovarian cancer. With the use of whole-genome analysis, the detection of possible location of critical tumor suppressor gene (TSGs) in the paired region of chromosomes has been identified, which are associated with BRCA1 and BRCA2 which further makes these novel molecular biomarkers as potential biomarkers. Moreover, studies are required to assess the combined use of traditional, molecular biomarkers that might be useful for enhanced sensitivity and specificity for early detection and prevention of ovarian cancer in early stages which will lead to reduced mortality and good prognosis

Ovarian Cancer Biomarkers: Moving Forward in Early Detection.

Ovarian cancer is a silent cancer which rate survival mainly relays in early stage detection. The discovery of reliable ovarian cancer biomarkers plays a crucial role in the disease management and strongly impact in patient's prognosis and survival. Although having many limitations CA125 is a classical ovarian cancer biomarker, but current research using proteomic or metabolomic methodologies struggles to find alternative biomarkers, using non-invasive our relatively non-invasive sources such as urine, serum, plasma, tissue, ascites or exosomes. Metabolism and metabolites are key players in cancer biology and its importance in biomarkers discovery cannot be neglected. In this chapter we overview the state of art and the challenges facing the use and discovery of biomarkers and focus on ovarian cancer early detection.

The Role of 3D Power Doppler in Screening for Ovarian Cancer

Background: It is clear that in developed countries more women die annually from ovarian cancer than from all other gynecologic malignancies combined. Objective: The aim of this article is to analyze current possibilities and propose adequate measures which can help the development of effective screening methods/assays for the early detection of epithelial ovarian cancer. Results and Discussion: This article updates the status of ovarian cancer screening and addresses most relevant studies published during the last five years. The developments that followed the review are best summarized in reference to the screening tests, target populations and newly published trials. The possible role of 3D ultrasound technology, especially 3D power Doppler imaging, in early and accurate detection of ovarian malignancy is discussed. We described our new ovarian cancer screening trial, which started in January 2001. Improvements in ultrasound technology such as 3D volume acquisition and 3D power Doppler imaging may have clinical utility in a more reliable identification of an abnormal ovarian vascularity and architecture. 3D volume acquisition allows for careful evaluation of the internal surfaces of cyst walls for excrescences otherwise not appreciated by 2D ultrasound. Conclusion: While the addition of 3D power Doppler provides a new tool for measuring the quality of ovarian tumor angiogenesis, improving accurate diagnosis of ovarian malignancies, its clinical value for the early detection of ovarian carcinoma has yet to be determined.

Zinc as an auxiliary marker along with Cancer Antigen 125 in ovarian cancer

Ovarian cancer is the most common and most lethal gynecologic malignancy. It is one of the most leading cancers in Indian women. The urge for the early detection of ovarian cancer continues to be one of the most important issues in women’s health care. The cause for ovarian cancer may be due to increased oxidative stress, heredity, dietary deficiency etc. As zinc is essential for cytotoxic/tumor suppressor effect and it plays very important role in cancer progression. In ovarian cancer the level of zinc in blood is usually decreased. So, the hypothesis of the study is to know the association between the serum zinc levels and the ovarian cancer marker, CA125. Aim of the study is to correlate the serum Zinc levels with serum CA 125 in healthy controls and ovarian cancer subjects. Totally 90 subjects are enrolled in the study. Out of this 74 were controls and 16 were ovarian cancer subjects. The serum CA 125 was increased in ovarian cancer patients compared to controls. Whereas, serum Zinc was decreased in ovarian cancer patients compared to controls. As well as there was indeed a strong association of serum Zinc and CA 125 in ovarian cancer patients. Hence measurement of serum Zinc, an inexpensive assay could be used as an auxiliary marker along with CA 125 in screening of ovarian cancer. Keywords: Zinc, Ovarian cancer, Marker CA 125, Serum CA 125.

Abstract DP-015: BIOTINYLATED ESTROGENS A NOVEL TOOL FOR EARLY DETECTION OF ADDUCT IN OVARIAN CANCER

Abstract Elevated estrogens exert their carcinogenic effects by at least three different mechanisms; they promote cell proliferation by transcriptional regulation of estrogen responsive genes, cause generation of reactive oxygen species and other free radicals, and directly react with DNA and form potentially mutagenic adducts. However, unbalanced estrogen metabolism has been linked to development of several malignant diseases including breast, endometrial and ovarian cancer and has been identified as a risk factor for these cancers. The metabolic breakdown of estogens is regulated by a series of reactions mediated by hepatic and peripheral enzymes that balances the induction and reduction of cellular stress. An imbalance in this enzymes and processes can lead to highly reactive catechol estrogen metabolites that can react with DNA, form carcinogenic DAN-adducts and lesions. Although several studies established a connection between estrogen-induced DNA damage and carcinogenesis, the underlying molecular mechanisms have been difficult to study because of the technical challenges in detecting and analyzing the variety of different DNA lesions that are formed by estrogen compounds. Moreover, detection and analysis of these adducts are important to directly monitor estrogen metabolites induced cellular responses in the cells. Towards this, we developed a novel method using biotinylated-estrogens that allows immunodetection of estrogen-induced DNA adducts by Slot-blot and single-cell molecular combing and proximity ligation assays. Using these modified estrogens we first time quantitatively detected these adducts on DNA by immune Slot-blot techniques and on DNA fibers. Furthermore, similar to other environmental carcinogens estrogens activates replication associated DNA damage responses and induces chromosomal instability. Hence, first time our studies demonstrate that biotin-labeled estrogens could be a powerful tool to detect estrogen adducts and to probe associated DNA damage responses and cellular responses. Citation Format: Kaushlendra Tripathi, Chinnadurai Mani, David W. Clark, Komaraiah Palle. BIOTINYLATED ESTROGENS A NOVEL TOOL FOR EARLY DETECTION OF ADDUCT IN OVARIAN CANCER [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr DP-015.

Abstract AP07: PROTEIN AND IMAGING MARKERS FOR EARLY DETECTION OF EPITHELIAL OVARIAN CANCER

Abstract A central problem in ovarian cancer is late diagnosis, where the 5-year survival rate plummets well below 50%. It is now believed that a significant fraction of ovarian high grade serous carcinoma (HGSC) may actually start in the fallopian tubes (FTs), and that precancerous changes are detectable before metastasis to the ovary and peritoneal cavity occurs. A recently published molecular evolutionary analysis identifies a window of 7 years between development of a serous tubal intraepithelial carcinoma (STIC) and initiation of ovarian carcinoma, with metastases following rapidly thereafter. The authors are working to address the unmet clinical need for a minimally invasive test for early (pre-metastatic) ovarian cancer. Existing whole-body imaging techniques and transvaginal ultrasound have thus far displayed inadequate resolution and sensitivity, however optical imaging methods could fulfill the criteria for detection of primary HGSC when it is still located in the FTs and before it has spread to the ovaries. We have shown that two optical imaging modalities, optical coherence tomography (OCT) and multispectral fluorescence imaging (MFI) have great promise for detection of ovarian and FT abnormalities. In a small ex-vivo study, we found that 5 MFI measurements were sufficient to distinguish between normal, cancerous, and benign FT and ovary tissue with 100% sensitivity and specificity. We used laparoscopic OCT in an in-vivo study of 17 women and revealed distinct image features for normal, cancerous, and benign abnormalities of the ovary. For minimally invasive imaging of the fallopian tubes, a sub-millimeter diameter, flexible, steerable endoscope is necessary in order to navigate through the natural orifice of the ostium in the uterus. We have recently prototyped the smallest (0.8 mm diameter) OCT/MFI imaging endoscope with a forward-viewing imaging channel. The system as tested has approximately 70 degree full field of view, a working distance from 1 mm to infinity, and resolution that varies from 35 µm at 1 mm to 180 µm at 10 mm working distance. Such an imaging test is minimally invasive however not appropriate for wholesale screening of the general population. Therefore, we propose to utilize it as an adjunct confirmatory test after an initial positive or suspicious blood test. Our preliminary data indicate that there are significant changes in serum protein biomarkers in HGSC cases more than 18 months before diagnosis. We have identified FBG and PF4 as pre-diagnostic biomarkers of HGSC with 18-84 months lead time, and have generated and validated a 3-biomarker panel (FBG, PF4, and CA125) that classifies HGSC with >80% sensitivity/>70% specificity and 18-84 months lead time. We have identified overexpression of several glycolytic enzymes in STIC lesions and in human pre-diagnostic serum samples, indicating potential usefulness of these proteins as screening biomarkers and potential utility of glycolysis as imaging biomarker of STIC lesion. Our continuing work is focused on refining the serum protein biomarker sensitivity and specificity, creating a second-generation falloposcope for a first-in-women feasibility study, and creating an integrated model that incorporates both sets of data into an early EOC detection method. Citation Format: Jennifer K. Barton, Anna E. Lokshin, David A. Fishman, John F. Black. PROTEIN AND IMAGING MARKERS FOR EARLY DETECTION OF EPITHELIAL OVARIAN CANCER [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr AP07.

Abstract DP-001: KEY ACHIEVEMENT OF THE FAST PADE TRANSFORM IN MAGNETIC RESONANCE SPECTROSCOPY FOR EARLY OVARIAN CANCER DIAGNOSTICS

Abstract PURPOSE: An excellent candidate for early ovarian cancer detection would be magnetic resonance spectroscopy (MRS), being non-invasive, ionizing-radiation-free, with the potential to identify metabolic features of cancer. To succeed, encoded MRS time signals must be adequately processed. This has not been feasible in clinical MRS which relies upon the fast Fourier transform (FFT), generating low-quality, poorly-informative spectra, with very few metabolites identified. Our meta-analysis shows that cancerous and benign ovarian lesions are inadequately distinguished via FFT-based MRS. Our advanced signal processor, the fast Pade transform (FPT) has high-resolution capacity and is quantification-equipped. We highlight key achievements of FPT-based MRS for ovarian cancer diagnostics. EXPLANATION OF THE DATA: In studies on noisy in-vitro type MRS data associated with benign and cancerous ovary, the parametric FPT was benchmarked, precisely reconstructing all physical spectral parameters with extremely high resolution. The parametric FPT was successfully applied to MRS time signals encoded in-vivo from serous cystic ovarian tumor. Noise was separated out, to identify and quantify densely-packed, often overlapping genuine spectral components. These include recognized and possible cancer biomarkers: phosphocholine, myoinositol, isoleucine, valine, lactate, threonine, alanine, among some 90 metabolites in a narrow spectral range-of-interest. Nearly all these metabolites remain undetected with Fourier-based in-vivo MRS of the ovary. The previously unexplored properties of the non-parametric derivative FPT (dFPT) have been benchmarked for detection and quantification of phosphocholine, a key biomarker of ovarian cancer and other malignancies. This is a very demanding task for this shape estimation, since phosphocholine is invisible in customary non-derivative envelopes. The dFPT solves this problem, clearly identifying and quantifying all genuine resonances, including phosphocholine. Thereby, on the same screen, phosphocholine is visualized, as are the concentrations and other peak signatures for all the other metabolites. Thus, the higher-order differentiation transform in the dFPT simultaneously enhances resolution, suppresses noise and exactly quantifies, despite non-parametric processing of envelope lineshapes alone. In sharp contrast, even at low differentiation order, the derivative FFT hugely amplifies noise, losing all genuine information. With increased derivative order, the non-parametric dFPT exactly reconstructs the components of the parametric dFPT. The peak signatures (positions, heights, widths) reconstructed by the non-parametric dFPT in the magnitude mode are uniquely related to the absorptive non-derivative parametric FPT. This permits straightforward interpretation and extraction of peak area and associated metabolite concentrations. Thus, in the performed benchmarking, the higher-order non-parametric dFPT is a stand-alone method for clear display with identification and exact quantification of key metabolic information, including for the ovarian cancer biomarker phosphocholine. CONCLUSIONS: Derivative magnetic resonance spectroscopy provides clearly interpretable spectra for clinicians, with all needed quantitative information readily at-hand. Being computationally fast, with robust noise suppression, the dFPT is poised to be implemented in clinical scanners. These proof-of-concept studies with in-vitro type data justify pursuing this strategy in-vivo for ovarian cancer diagnostics. We anticipate that the high-order non-parametric dFPT will be the stand-alone method-of-choice for streamlined detection and exact quantification of key ovarian cancer biomarkers for in-vivo encoded MRS time signals. Work is underway to carry-out these next steps. Note: This abstract was not presented at the symposium. Citation Format: Dzevad Belkic, Karen Belkic. KEY ACHIEVEMENT OF THE FAST PADE TRANSFORM IN MAGNETIC RESONANCE SPECTROSCOPY FOR EARLY OVARIAN CANCER DIAGNOSTICS [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr DP-001.

Human epididymis protein 4 antigen-autoantibody complexes complement cancer antigen 125 for detecting early-stage ovarian cancer.

Early detection of ovarian cancer could significantly improve patient outcomes. Cancer antigen 125 (CA 125) is elevated in sera from approximately 60% of patients with early-stage (I/II) disease. Sensitivity might be improved through the combination of CA 125 with other biomarkers. Among potential biomarkers, antigen-autoantibody (Ag-AAb) complexes have received relatively little attention. Luminex-based immunoassays were used to measure human epididymis protein 4 (HE4), anti-HE4 autoantibody, and HE4 Ag-AAb complexes in sera from patients with early- (n=73) and late-stage ovarian cancers (n=49) at the time of diagnosis and from asymptomatic women with (n=15) or without ovarian cancer (n=212) enrolled in the Normal Risk Ovarian Cancer Screening Study. At 98% specificity for healthy, asymptomatic women, 7% of patients with early-stage (I/II) ovarian cancer and 4% of patients with late-stage (III/IV) disease had elevated levels of HE4 autoantibody, whereas elevated levels of HE4 Ag-AAb complexes were detected in sera from 38% of early-stage cases and 31% of late-stage cases. Complementarity was observed in receiver operating characteristic (ROC) curves between HE4 Ag-AAb complexes and CA 125 levels in early-stage ovarian cancer (P<.001). CA 125 detected 63% of cases, and a combination of CA 125 and HE4 Ag-AAb complexes detected 81%. Complementarity was also observed in ROC curves for an independent validation set with 69 early-stage patients (P=.039). HE4 Ag-AAb complexes were detected in serial preclinical serum samples from women destined to develop ovarian cancer: they correlated with CA 125 but did not provide a lead time. HE4 Ag-AAb complexes could complement CA 125 in detecting a higher fraction of early-stage ovarian cancers.

Ovarian Cancer Animal Models for Preclinical Studies and Development of Ovarian Cancer Drugs

Treatment for ovarian carcinoma is still far from optimal, animal models are still needed to study human epithelial ovarian cancer. Animal models of ovarian cancer are very important for understanding the pathogenesis of the disease and for testing new treatment strategies. Ovarian carcinogenesis models in mice have been modified and repaired to produce preneoplastic lesions and neoplastic ovaries that are pathogens resembling human ovarian cancer. Although spontaneous ovarian tumors in mice have been reported, some of the shortcomings of existing studies preclude their use as animal models of ovarian cancer. Because of this, many efforts have been made to develop animal models that are relevant for ovarian cancer. Experimental animal models are developed accurately to represent cellular and molecular changes associated with the initiation and development of human ovarian cancer. Accurate experimental models have significant potential in facilitating the development of better methods for early detection and treatment of ovarian cancer. Several animal models of ovarian cancer have been reported, including manipulation of various reproductive factors or exposure to carcinogens. The latest advance in ovarian cancer modeling is using genetically engineered mice.

High Resolution Based Quantitative Determination of Methylation Status of CDH1 and VIM Gene in Epithelial Ovarian Cancer.

Background:DNA promoter methylation is widely explored epigenetic phenomena, known to effect gene expression and further perturbation in cellular homeostasis. Myriad of studies have leveraged promoter methylation and its potential as biomarker for various types of cancer. Aim of present study is to investigate promoter methylation of CDH1 and VIM gene and etiology of epithelial ovarian cancer (EOC). Methods:Most of previous studies were qualitative; we have quantitatively assessed methylation levels in 50 EOC cases and control each through high recognition melt (HRM) technique. Results:At 10 % cutoff for CDH1 94% of EOC cases were found to be methylated with mean methylation of 45±13.8, whereas for control mean methylation was found to be 7.3±3.7 amongst 16 % methylation positive control samples. For VIM methylation was detected in 96% of cases with mean of 50.44±11.7 in EOC and in 12% methylation positive samples for control mean methylation was 6.24±4.3. Conclusion:In short HRM based DNA methylation can serve as a robust and sensitive diagnostic method for promoter methylation detection and as a biomarker for early epithelial ovarian cancer detection.

Quantification of multiphoton and fluorescence images of reproductive tissues from a mouse ovarian cancer model shows promise for early disease detection.

.Ovarian cancer is the deadliest gynecologic cancer due predominantly to late diagnosis. Early detection of ovarian cancer can increase 5-year survival rates from 40% up to 92%, yet no reliable early detection techniques exist. Multiphoton microscopy (MPM) is a relatively new imaging technique sensitive to endogenous fluorophores, which has tremendous potential for clinical diagnosis, though it is limited in its application to the ovaries. Wide-field fluorescence imaging (WFI) has been proposed as a complementary technique to MPM, as it offers high-resolution imagery of the entire organ and can be tailored to target specific biomarkers that are not captured by MPM imaging. We applied texture analysis to MPM images of a mouse model of ovarian cancer. We also conducted WFI targeting the folate receptor and matrix metalloproteinases. We find that texture analysis of MPM images of the ovary can differentiate between genotypes, which is a proxy for disease, with high statistical significance (). The wide-field fluorescence signal also changes significantly between genotypes (). We use the features to classify multiple tissue groups to over 80% accuracy. These results suggest that MPM and WFI are promising techniques for the early detection of ovarian cancer.

Detection of early stage ovarian cancer in a large community cohort.

BackgroundAlthough detecting ovarian cancer at early stage is a highly meaningful clinical goal, no studies have evaluated early stage disease presentation in a large community‐based population and how it differs from that of late stage disease.MethodsElectronic medical records were evaluated for women diagnosed with ovarian or fallopian tube cancer in 2016 and 2017 to identify the first imaging study to detect disease. Women being followed prior to diagnosis for known genetic risk from BRCA or other mutation were excluded. The visit in which the imaging test was ordered and related encounters were reviewed to determine the indication for imaging. Patient characteristics, presenting symptoms and duration, and modality of first abnormal imaging were compared for early vs late stage ovarian cancer and by provider specialty.ResultsOf 540 women with ovarian cancer, 190 (35%) were diagnosed with early stage disease, of whom 141 (74%) were symptomatic, with 45% of women presenting to internists, 33% to gynecologists, and 20% to emergency medicine physicians. Pelvic ultrasonography detected only 23% of late stage cases whereas pelvic ultrasonography and abdominal pelvic computed tomography (CT) each detected 47% of early stage cases. While abdominal pain and bloating were common to both women with early and late stage cancer, women with early stage disease were younger (58 vs 64 years, P < .0001), more likely to present to gynecologists (33% vs 15%, P < .001) and complained more often of a palpable mass (17% vs 6%, P < .0001) or postmenopausal bleeding (11% vs 5%, P < .001).ConclusionsExcluding women with genetic predisposition to ovarian cancer known prior to diagnosis, approximately three out of four cases of early stage ovarian cancer are detected as the result of evaluation of symptoms and one in four cases are detected incidentally. Abdominal pelvic CT and pelvic ultrasonography each detect an equal proportion of early stage cases. In contrast to late stage presentation, women diagnosed with early stage disease present more often with complaints of a palpable mass or postmenopausal bleeding, particularly to gynecologists.

Reply to Comment on “Osteopontin, Macrophage Migration Inhibitory Factor and Anti-Interleukin-8 Autoantibodies Complement CA125 for Detection of Early Stage Ovarian Cancer” Cancers 2019, 11, 596: Markers for Early Detection of Ovarian Cancer

We appreciate Mor et al [...].

Techniques Associated with Exosome Isolation for Biomarker Development: Liquid Biopsies for Ovarian Cancer Detection.

Ovarian cancer is the leading gynecological malignancy worldwide. This is attributed to the fact that the disease is often diagnosed at an advanced stage, where the survival rates drop from approximately 90% (detection at an early stage) to 20%. Furthermore, ovarian cancer is not associated with overt physical symptoms. Thus, there is an urgent need for a highly sensitive and minimally invasive biomarker for the early detection of ovarian cancer. However, this continues to remain an unmet clinical need, as several proposed techniques have shown low sensitivity and specificity, with poor positive and negative predictive values. The quest for an ideal biomarker has bought exosomes to the forefront. Exosomes are small extracellular vesicles of an endocytic origin, which can encapsulate genetic information, in the form of proteins and miRNAs. They are released by multiple cell types and are involved in intercellular communication, through the transfer of their cargo. The process of exosome biogenesis allows for the packaging of molecules from both membranous and cytosolic origins. Therefore, exosomes are representations of the releasing cell, and thus provide an insight into the cellular environment. Furthermore, exosomal encapsulation of molecules such as proteins and miRNAs can prevent degradation, making exosomes an ideal biomarker source. Thus, this chapter provides an overview of ovarian cancer, the potential of exosomes as an early detection biomarker, and the different methods associated with the isolation of different vesicle subpopulations, and exosome enrichment.

Comment on "Osteopontin, Macrophage Migration Inhibitory Factor and Anti-Interleukin-8 Autoantibodies Complement CA125 for Detection of Early Stage Ovarian Cancer" Cancers 2019, 11, 596: Markers for Early Detection of Ovarian Cancer.

We read with interest the recent publication by Guo et al [...].

Meeting report from the 2018 12th Biennial Ovarian Cancer Research Symposium detection and prevention of ovarian cancer

The objective of this review is to summarize recent research advances in the detection and prevention of ovarian cancer and discuss the experts’ opinions of future directions. The 12th Biennial...

Novel Approaches to Ovarian Cancer Screening.

Both conventional and novel approaches to early detection of ovarian cancer are reviewed in the context of new developments in our understanding of ovarian cancer biology. While CA125 as a single value lacks adequate specificity or sensitivity for screening, large studies have shown that a 2-stage strategy which tracks CA125 change over time and prompts transvaginal ultrasound (TVS) for a small subset of women with abnormally rising biomarker values achieves adequate specificity and detects a higher fraction of early-stage disease. Sensitivity could clearly be improved in both blood tests and in imaging. Metastasis can occur from ovarian cancers too small to increase blood levels of protein antigens and a significant fraction of ovarian cancers arise from the fimbriae of fallopian tubes that cannot be imaged with TVS. Autoantibodies, miRNA, ctDNA, DNA methylation in blood, and cervical mucus might improve sensitivity of the initial phase and magnetic relaxometry and autofluorescence could improve imaging in the second phase. Enhancing the sensitivity of two-stage strategies for early detection could reduce mortality from ovarian cancer.

Abstract 912: Macrophage inhibitory factor (MIF), osteopontin (OPN) and anti-interleukin-8 (IL-8) autoantibodies (AAb) complement CA125 for detection of early-stage ovarian cancer

Abstract Background: Early detection of ovarian cancer promises to reduce mortality. At present, only 20 percent of ovarian cancer is found in early stage (I-II). CA125 is found in sera from approximately 60% of patients with early stage disease. Greater sensitivity could be observed with a panel of blood tests. Methods: A panel of 10 antigen biomarkers (MIF, Leptin, IL-6, IL-8, TNFa, OPN, FGF2, HE4, TGFa and a panel of autoantibodies (AAbs) against 12 antigens (IL-8, MDM2, c-myc, PLAT, EpCAM, HOXA7, ENO1, PDI, HSPA5, HSPA8, ANXA2, Cathepsin D) were analyzed in sera of 77 ovarian cancer patients with early stage (I-II), 50 patients with late stage (III-IV), and 216 healthy women from the Normal Risk Ovarian Cancer Screening Study (NROSS) using Luminex-based immunoassays. Serum levels of serum tumor marker CA-125 were routinely measured in all patients using a Roche assay. The most promising markers (CA125, MIF, OPN, and anti-IL-8 autoantibodies were validated using an independent panel with sera from 69 early stage and 50 late ovarian cancer patients and 200 healthy controls. Result: Serum level of CA125, MIF, OPN and IL-8 AAb were elevated in early stage (I-II) and late stage (III-IV) ovarian cancer patients compared with healthy controls. Analyzing the positive biomarkers in combination with CA125 increased detection of early stage disease from 62% with CA125 alone to 92% a panel of CA125, MIF, OPN and IL-8 AAb at 98% specificity. For patients with late stage disease sensitivity increased from 90% to 98% with the panel. Complementarity of CA125 with MIF, OPN and IL-8 AAb was confirmed with an independent validation set, where sensitivity for early stage disease was improved from 84% to 91% at 98% specificity. Conclusion: MIF, OPN and IL8 AAb could be used in combination with CA125 to distinguish ovarian cancer patients from health controls with high sensitivity. Citation Format: Jing Guo, Wei-lei Yang, Joseph Celestino, Karen Lu, Anna E. Lokshin, Zhen Lu, Robert C. Bast. Macrophage inhibitory factor (MIF), osteopontin (OPN) and anti-interleukin-8 (IL-8) autoantibodies (AAb) complement CA125 for detection of early-stage ovarian cancer [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 912.