Special Issue "Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment"

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 December 2019).

Special Issue Editor

Dr. Edward J. Pavlik
Website
Guest Editor
Director of Ovarian Screening Research in Gynecologic Oncology, University of Kentucky College of Medicine, Lexington, KY 40536-0298, USA
Interests: ovarian cancer; cancer screening; tumor imaging
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Ovarian cancer is deadly, claiming more women than all other gynecological malignancies combined. However, when detected at an early stage, ovarian cancer is highly curable. Consequently, screening efforts are likely to be the best way to detect early stage disease. The forthcoming Special Issue focuses on several key elements that are essential for an understanding of ovarian cancer, its characteristics, and risk factors that are relevant to screening for ovarian cancer. Invited topics that are:

  1. Risk factors for ovarian cancer.
  2. Markers and new genes associated with ovarian cancer.
  3. Ovarian cancer subtypes and their relatedness.
  4. Treatment related to high volume centers and National Comprehensive Cancer Network guidelines.
  5. Predictors of treatment responses.
  6. Treatment costs and effectiveness.
  7. Therapies and precision therapies for ovarian cancer.
  8. Vaccines and checkpoints in the immune therapy of ovarian cancer.
  9. Diagnostic tools: Strengths and limitations.
  10. International variations in ovarian cancer diagnosis and treatment.
  11. Determining ovarian cancer risk by tests for the general population.
  12. Mitigating risk of ovarian cancer surgically or medically.
  13. Screening trial design: Selection, make-up, execution, protocol driven aspects, age of participants, duration of screening, follow-up and events to be censored.
  14. Collateral affectors in screening: Perceptions of well-being and potential complications of treatment as confounders of compliance.
  15. Endpoints and efficacy: Early stage detection, disease specific survival, overall survival and avoidance of an ovarian cancer death as endpoints, with considerations of screen   performance and cost.
  16. Interpretation of ovarian screening trials. Comparisons between screening trials conducted in the United States, the United Kingdom and Japan are informative regarding the current status of ovarian screening.
Dr. Edward J. Pavlik
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • ovarian cancer
  • risk
  • treatment
  • detection
  • screening
  • trail design
  • treatment
  • collateral affectors
  • endpoints
  • costs
  • efficacy

Related Special Issues

Published Papers (24 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review, Other

Open AccessArticle
Olaparib Combined with an ATR or Chk1 Inhibitor as a Treatment Strategy for Acquired Olaparib-Resistant BRCA1 Mutant Ovarian Cells
Diagnostics 2020, 10(2), 121; https://doi.org/10.3390/diagnostics10020121 - 22 Feb 2020
Cited by 7
Abstract
Objective: Despite the promise of PARP inhibitors (PARPi) for treating BRCA1/2 mutated ovarian cancer (OC), drug resistance invariably develops. We hypothesized rationale drug combinations, targeting key molecules in DNA repair pathways and the cell cycle may be synergistic and overcome acquired PARPi resistance. [...] Read more.
Objective: Despite the promise of PARP inhibitors (PARPi) for treating BRCA1/2 mutated ovarian cancer (OC), drug resistance invariably develops. We hypothesized rationale drug combinations, targeting key molecules in DNA repair pathways and the cell cycle may be synergistic and overcome acquired PARPi resistance. Methods: Drug sensitivity to PARPi alone and in combination with inhibitors of key DNA repair and cell cycle proteins, including ATR (VE-821), Chk1 (MK-8776), Wee1 (MK-1775), RAD51 (RI-1) was assessed in PARPi-sensitive (UWB1) and -resistant (UWB1-R) gBRCA1 mutant OC cell lines using a cell proliferation assay. The Bliss synergy model was used to estimate the two-drug combination effect and pharmacologic synergy (Bliss score ≥ 0) or antagonistic (Bliss score ≥ 0) response of the PARPi in combination with the inhibitors. Results: IC50 for olaparib alone was 1.6 ± 0.9 µM compared to 3.4 ± 0.6 µM (p = 0.05) for UWB1 and UWB1-R cells, respectively. UWB1-R demonstrated increased sensitivity to ATRi (p = 0.04) compared to UWB1. Olaparib (0.3–1.25 µM) and ATRi (0.8–2.5 µM) were synergistic with Bliss scores of 17.2 ± 0.2, 11.9 ± 0.6 for UWB1 and UWB1-R cells, respectively. Olaparib (0.3–1.25 µM) and Chk1i(0.05–1.25 µM) were synergistic with Bliss scores of 8.3 ± 1.6, 5.7 ± 2.9 for UWB1 and UWB1-R cells, respectively. Conclusions: Combining an ATRi or Chk1i with olaparib is synergistic in both PARPi-sensitive and -resistant BRCA1 mutated OC cell models, and are rationale combinations for further clinical development. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Show Figures

Figure 1

Open AccessCommunication
Accuracy in Referrals to Gynecologic Oncologists Based on Clinical Presentation for Ovarian Mass
Diagnostics 2020, 10(2), 106; https://doi.org/10.3390/diagnostics10020106 - 16 Feb 2020
Cited by 1
Abstract
Ovarian cancer is one of the most lethal gynecological cancers in women due to late diagnosis. Despite technological advancements, experienced physicians have high sensitivities and specificities in subjective assessments when combining ultrasound findings and clinical history in analyzing adnexal masses. This study aims [...] Read more.
Ovarian cancer is one of the most lethal gynecological cancers in women due to late diagnosis. Despite technological advancements, experienced physicians have high sensitivities and specificities in subjective assessments when combining ultrasound findings and clinical history in analyzing adnexal masses. This study aims to demonstrate general obstetricians and gynecologists’ (OB/GYN) appropriateness in gynecologic oncologist referrals for malignant ovarian masses based on history and physical (H&P), imaging, and available tumor markers. Three board certified OB/GYNs were given 148 cases and determined whether or not they would refer them to a gynecologic oncologist. Results showed that OB/GYNs were 81–85% accurate in diagnosing patients with a benign or malignant disease. Among the malignant cases, reviewers had a high sensitivity ranging from 74–81% in appropriately referring a malignancy. In our study, OB/GYNs referred between 23–32% of ovarian masses to a gynecologic oncologist with only 9.5% of cases found to be malignant. Despite the high referral rates, generalists showed a high degree of sensitivity in accurately referring malignant diseases based solely on clinical experience and imaging studies, which could improve survival rates with early intervention by gynecologic oncologists. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Open AccessArticle
Microsatellite Instability and MMR Genes Abnormalities in Canine Mammary Gland Tumors
Diagnostics 2020, 10(2), 104; https://doi.org/10.3390/diagnostics10020104 - 14 Feb 2020
Cited by 1
Abstract
Early diagnosis of mammary gland tumors is a challenging task in animals, especially in unspayed dogs. Hence, this study investigated the role of microsatellite instability (MSI), MMR gene mRNA transcript levels and SNPs of MMR genes in canine mammary gland tumors (CMT). A [...] Read more.
Early diagnosis of mammary gland tumors is a challenging task in animals, especially in unspayed dogs. Hence, this study investigated the role of microsatellite instability (MSI), MMR gene mRNA transcript levels and SNPs of MMR genes in canine mammary gland tumors (CMT). A total of 77 microsatellite (MS) markers in 23 primary CMT were selected from four breeds of dogs. The results revealed that 11 out of 77 MS markers were unstable and showed MSI in all the tumors (at least at one locus), while the other markers were stable. Compared to the other markers, the ABC9TETRA, MEPIA, 9A5, SCNA11 and FJL25 markers showed higher frequencies of instability. All CMT demonstrated MSI, with eight tumors presenting MSI-H. The RT-qPCR results revealed significant upregulation of the mRNA levels of cMSH3, cMLH1, and cPMSI, but downregulation of cMSH2 compared to the levels in the control group. Moreover, single nucleotide polymorphisms (SNPs) were observed in the cMSH2 gene in four exons, i.e., 2, 6, 15, and 16. In conclusion, MSI, overexpression of MMR genes and SNPs in the MMR gene are associated with CMT and could be served as diagnostic biomarkers for CMT in the future. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Show Figures

Figure 1

Open AccessArticle
Transmission of X-linked Ovarian Cancer: Characterization and Implications
Diagnostics 2020, 10(2), 90; https://doi.org/10.3390/diagnostics10020090 - 07 Feb 2020
Abstract
We recently reported evidence that a strong, BRCA-independent locus on the X-chromosome may contribute to ovarian cancer predisposition in families ascertained from the Familial Ovarian Cancer Registry (Buffalo, NY, USA). While it has been estimated that approximately 20% of all ovarian cancer cases [...] Read more.
We recently reported evidence that a strong, BRCA-independent locus on the X-chromosome may contribute to ovarian cancer predisposition in families ascertained from the Familial Ovarian Cancer Registry (Buffalo, NY, USA). While it has been estimated that approximately 20% of all ovarian cancer cases are hereditary, it is possible that a significant proportion of cases previously believed to be sporadic may, in fact, be X-linked. Such X-linked disease has a distinct pattern; it implies that a father will necessarily pass a risk allele to each of his daughters, increasing the prevalence of cancers clustered within a family. X-chromosome inactivation further influences the expression of X-linked alleles and may represent a novel target for screening and therapy. Herein, we review the current literature regarding X-linked ovarian cancer and interpret allele transmission-based models to characterize X-linked ovarian cancer and develop a framework for clinical and epidemiological familial ascertainment to inform the design of future studies. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Show Figures

Figure 1

Open AccessArticle
Socioeconomic Status and Ovarian Cancer Stage at Diagnosis: A Study Nested Within UKCTOCS
Diagnostics 2020, 10(2), 89; https://doi.org/10.3390/diagnostics10020089 - 07 Feb 2020
Abstract
Background: Tubo-ovarian cancer (OC) continues to be the most lethal of all gynaecological cancers. Over half of women are diagnosed with late stage (III/IV) disease, which has a five-year survival rate of 11%. Socioeconomic status (SES) has been shown to have an impact [...] Read more.
Background: Tubo-ovarian cancer (OC) continues to be the most lethal of all gynaecological cancers. Over half of women are diagnosed with late stage (III/IV) disease, which has a five-year survival rate of 11%. Socioeconomic status (SES) has been shown to have an impact on outcomes of several cancer types, including OC. This study aims to investigate any potential association between SES and stage at diagnosis of OC. Methods: Women from the non-screening arm of the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) with a confirmed diagnosis of OC prior to 01 January 2015 and an English index of multiple deprivation (IMD) score were eligible for the study. The association between IMD and OC stage (FIGO) was analysed using an ordinal logistic regression model adjusted for age at diagnosis and BMI. Results: Four-hundred and fifty seven women were eligible for inclusion in the primary analysis. The odds of being diagnosed with the higher dichotomization of stage (I vs. II/III/IV; I/II vs. III/IV; I/II/III vs. IV) was 1.29 (p = 0.017; 95% CI: 1.048–1.592) per unit SD (standard deviation) increase in IMD. This translates to a 29% increase in odds of being diagnosed at the higher stage per each unit SD increase in IMD. Conclusion: Increased deprivation is consistently associated with a higher probability of being diagnosed with later stage OC. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Show Figures

Figure 1

Open AccessArticle
Assessing the Costs of Screening for Ovarian Cancer in the United States: An Evolving Analysis
Diagnostics 2020, 10(2), 67; https://doi.org/10.3390/diagnostics10020067 - 25 Jan 2020
Abstract
The primary objective of this study is to provide an updated analysis of the cost of screening for ovarian cancer in the United States. Here, we use updated information from the University of Kentucky Ovarian Cancer Screening Trial in conjunction with new modifying [...] Read more.
The primary objective of this study is to provide an updated analysis of the cost of screening for ovarian cancer in the United States. Here, we use updated information from the University of Kentucky Ovarian Cancer Screening Trial in conjunction with new modifying factors such as U.S. national estimates of the cost of care (Truven Health MarketScan Database), recently published estimates of earnings lost due to ovarian cancer death and estimates of federal income taxes paid on those earnings. In total, 326,998 screens were performed during the Kentucky trial from 1987 to 2019. At a cost of $56 per screen, we estimate that the total base cost to operate the program over the last 32 years is $18,311,888. When accounting for the surgical cost of 381 false-positive cases, the total cost of the screening program increases by $3,030,474. However, these costs are offset by the benefit of treating more early-stage ovarian cancer in the screened population, with a total cost advantage of $4,016,475 at our institution (Kentucky) or $1,525,050 ($725,700–$3,312,650) (U.S.) nationally. Additionally, program costs are offset by approximately $3,549,000 due to the potential earnings gained by the 26 women whose lives have been saved with screening. Furthermore, the cost of the program is offset by the federal tax dollars paid on the recovered earnings and amounts to $383,292. Ultimately, the net adjusted total cost of the Kentucky screening program is an estimated $13,393,595 at our institution or $15,885,020 ($13,978,068–$16,799,083) nationally. Thus, the adjusted cost per screen is an estimated $40.96 in Kentucky or $48.58 ($42.75–$51.37) nationally. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Show Figures

Graphical abstract

Open AccessArticle
Disease-Specific Survival of Type I and Type II Epithelial Ovarian Cancers—Stage Challenges Categorical Assignments of Indolence & Aggressiveness
Diagnostics 2020, 10(2), 56; https://doi.org/10.3390/diagnostics10020056 - 21 Jan 2020
Cited by 1
Abstract
Epithelial ovarian cancers (EOC) consist of several sub-types based on histology, clinical, molecular and epidemiological features that are termed “histo-types”, which can be categorized into less aggressive Type I and more aggressive Type II malignancies. This investigation evaluated the disease-specific survival (DSS) of [...] Read more.
Epithelial ovarian cancers (EOC) consist of several sub-types based on histology, clinical, molecular and epidemiological features that are termed “histo-types”, which can be categorized into less aggressive Type I and more aggressive Type II malignancies. This investigation evaluated the disease-specific survival (DSS) of women with Type I and II EOC using histo-type, grade, and stage. A total of 47,789 EOC cases were identified in the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) data. Survival analysis and log rank test were performed to identify a 2-tiered classification (grade 1 vs. grade 2 & 3) for serous EOC. DSS of early stage serous EOC for grade 2 was significantly different from grade 3 indicating that a 2-tier classification for serous EOC applied only to late stage. DSS of Type I EOC was much better than Type II. However, DSS was 33–52% lower with late stage Type I than with early stage Type I indicating that Type I ovarian cancers should not be considered indolent. Early stage Type II EOC had much better DSS than late stage Type II stressing that stage has a large role in survival of both Type I and II EOC. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Show Figures

Figure 1

Open AccessArticle
Sarcopenic Factors May Have No Impact on Outcomes in Ovarian Cancer Patients
Diagnostics 2019, 9(4), 206; https://doi.org/10.3390/diagnostics9040206 - 28 Nov 2019
Cited by 4
Abstract
Although the prognostic value of sarcopenic factors, such as loss of muscle mass and quality, have been widely reported in patients with cancer during the last decade, the value in those with ovarian cancer remains unclear. Therefore, this study evaluated the prognostic impact [...] Read more.
Although the prognostic value of sarcopenic factors, such as loss of muscle mass and quality, have been widely reported in patients with cancer during the last decade, the value in those with ovarian cancer remains unclear. Therefore, this study evaluated the prognostic impact of sarcopenic factors in patients with ovarian cancer. We retrospectively evaluated the data of 94 ovarian cancer patients who underwent surgery and chemotherapy at the Shimane University Hospital between March 2006 and 2013. Preoperative computed tomography scan at the level of the third lumbar vertebra was used to evaluate skeletal muscle volume and quality based on the skeletal muscle index (SMI) and intramuscular adipose tissue content (IMAC), respectively. The impact of preoperative SMI and IMAC on outcomes was subsequently investigated. Low SMI and high IMAC were not significantly associated with disease-free survival (p = 0.329 and p = 0.3370, respectively) or poor overall survival (p = 0.921 and p = 0.988, respectively). Neither preoperative low muscle volume nor low muscle quality was a poor prognostic factor in ovarian cancer. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Show Figures

Figure 1

Open AccessCommunication
Overall Survival and Adjuvant Therapy in Women with Ovarian Carcinosarcoma: A Single-Institution Experience
Diagnostics 2019, 9(4), 200; https://doi.org/10.3390/diagnostics9040200 - 22 Nov 2019
Cited by 1
Abstract
Background: Carcinosarcoma of the ovary (CSO) is a rare and aggressive variant of ovarian cancer. Due to the rare nature of the disease there is insufficient evidence to make recommendations regarding standard management and overall prognosis. Methods: An Institutional Review Board-approved study identified [...] Read more.
Background: Carcinosarcoma of the ovary (CSO) is a rare and aggressive variant of ovarian cancer. Due to the rare nature of the disease there is insufficient evidence to make recommendations regarding standard management and overall prognosis. Methods: An Institutional Review Board-approved study identified all our patients with CSO between January 2011 and May 2018. Demographic and outcome measures were abstracted from the medical records and tumor board files. Cox proportional hazard models, log rank tests, and comparisons of means were used to calculate significance (p < 0.05). Results: 27 women with CSO were identified. The median age at diagnosis was 65 years (range 48–91). Five women (18%) presented with early stage disease (Stage I or II) and 22 patients (82%) presented with late stage III or IV disease. Twenty patients (74%) received intravenous platinum-based combination chemotherapy. Seven patients did not receive chemotherapy during their treatment course. The median overall survival was 23 months (range 2–68 months). Overall survival was not significantly worsened by the stage of disease at diagnosis. There was no difference in survival based on the age at diagnosis, tobacco status or ethnicity (p > 0.05). Conclusion: This is one of the largest single institution experiences with CSO. The majority of our patients presented with advanced stage disease and received adjuvant platinum-based chemotherapy after cytoreductive surgery. The median overall survival of 23 months was not affected by the stage of the disease. The optimal management of this rare disease needs further study with collaborative, prospective multi-institutional trials. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Show Figures

Figure 1

Open AccessArticle
Ovarian Cancer Targeting Phage for In Vivo Near-Infrared Optical Imaging
Diagnostics 2019, 9(4), 183; https://doi.org/10.3390/diagnostics9040183 - 10 Nov 2019
Cited by 1
Abstract
Ovarian cancer is often diagnosed at late stages due to current inadequate detection. Therefore, the development of new detection methods of ovarian cancer is needed. This may be achieved by phage nanoparticles that display targeting peptides for optical imaging. Here, two such phage [...] Read more.
Ovarian cancer is often diagnosed at late stages due to current inadequate detection. Therefore, the development of new detection methods of ovarian cancer is needed. This may be achieved by phage nanoparticles that display targeting peptides for optical imaging. Here, two such phage clones are reported. Ovarian cancer binding and specificity of phage clones (pJ18, pJ24) and peptides (J18, J24) were investigated using fluorescent microscopy and modified ELISA. Further, AF680-labeled phage particles were subjected to biodistribution and optical imaging studies in SKOV-3 xenografted mice. Fluorescent microscopy and ELISA of phage and peptides showed significantly increased binding to SKOV-3 cells compared to controls. Additionally, these studies revealed that J18 exhibits specificity for ovarian cancer SKOV-3 and OVCAR-3 cell lines. Further, peptides displayed increased SKOV-3 binding compared to N35 (non-relevant peptide) with EC50 values of 22.2 ± 10.6 μM and 29.0 ± 6.9 (mean ± SE), respectively. Biodistribution studies of AF680-labeled phage particles showed tumor uptake after 4 h and excretion through the reticuloendothelial system. Importantly, SKOV-3 tumors were easily localized by optical imaging after 2 h and 4 h and displayed good tumor-to-background contrast. The fluorescent tumor signal intensity was significantly higher for pJ18 compared to wild type (WT) after 2 h. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Show Figures

Figure 1

Open AccessArticle
BRCA1/2 Molecular Assay for Ovarian Cancer Patients: A Survey through Italian Departments of Oncology and Molecular and Genomic Diagnostic Laboratories
Diagnostics 2019, 9(4), 146; https://doi.org/10.3390/diagnostics9040146 - 09 Oct 2019
Cited by 1
Abstract
In Italy, 5200 new ovarian cancers were diagnosed in 2018, highlighting an increasing need to test women for BRCA1/2. The number of labs offering this test is continuously increasing. The aim of this study was to show the results coming from the [...] Read more.
In Italy, 5200 new ovarian cancers were diagnosed in 2018, highlighting an increasing need to test women for BRCA1/2. The number of labs offering this test is continuously increasing. The aim of this study was to show the results coming from the intersociety survey coordinated by four different Clinical and Laboratory Italian Scientific Societies (AIOM, SIAPEC-IAP, SIBIOC, and SIGU). A multidisciplinary team belonging to the four scientific societies drew up two different questionnaires: One was targeted toward all Italian Departments of Medical Oncology, and the second toward laboratories of clinical molecular biology. This survey was implemented from September 2017 to March 2018. Seventy-seven out of 305 (25%) Departments of Medical Oncology filled our survey form. Indeed, 59 molecular laboratories were invited. A total of 41 laboratories (70%) filled in the questionnaire. From 2014 to 2017, 16 new molecular laboratories were activated. A total of 12,559 tests were performed in the year 2016, with a mean of 339 tests and a median of 254 tests per laboratory, showing a glimpse of an extreme low number of tests performed per year by some laboratories. In terms of the type and number of professionals involved in the pre- and post-test counseling, results among the onco-genetic team were heterogeneous. Our data show that the number of laboratories providing BRCA1/2 germline assays is significantly increased with further implementation of the somatic test coming soon. The harmonization of the complete laboratory diagnostic path should be encouraged, particularly in order to reduce the gap between laboratories with high and low throughput. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Show Figures

Figure 1

Open AccessArticle
Psychological Response to a False Positive Ovarian Cancer Screening Test Result: Distinct Distress Trajectories and Their Associated Characteristics
Diagnostics 2019, 9(4), 128; https://doi.org/10.3390/diagnostics9040128 - 25 Sep 2019
Cited by 1
Abstract
Routine screening for ovarian cancer (OC) can yield an abnormal result later deemed benign. Such false positive (FP) results have been shown to trigger distress, which generally resolves over time. However, women might differ in the trajectory of the distress experience. Women participating [...] Read more.
Routine screening for ovarian cancer (OC) can yield an abnormal result later deemed benign. Such false positive (FP) results have been shown to trigger distress, which generally resolves over time. However, women might differ in the trajectory of the distress experience. Women participating in a routine OC screening program (n = 373) who received an abnormal screening result completed a baseline assessment prior to a follow-up screening test to clarify the nature of their abnormal result. All women were subsequently informed that no malignancy was present, and follow-up assessments were completed one and four months post-baseline. Demographic, clinical, dispositional (optimism, monitoring), and social environmental (social constraint, social support) variables were assessed at baseline. OC-specific distress was assessed at all three assessments. Trajectory analyses identified three distress trajectories differing in the baseline level of distress. A high decreasing trajectory, representing about 25% of women, was characterized by high levels of distress at baseline with distress declining over time, but still elevated at four-month follow-up. In contrast, a no distress trajectory group, representing about 30% of women, was characterized by essentially no distress at any time point. Principal risk factors for membership in the high decreasing trajectory group included a family history of OC, lower dispositional optimism, and greater social constraint. These risk factors could be used to target resources efficiently towards managing women at risk for potentially clinically-significant distress after receipt of an FP OC screening test. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Show Figures

Figure 1

Open AccessArticle
Mining Featured Biomarkers Linked with Epithelial Ovarian CancerBased on Bioinformatics
Diagnostics 2019, 9(2), 39; https://doi.org/10.3390/diagnostics9020039 - 09 Apr 2019
Cited by 1
Abstract
Epithelial ovarian cancer (EOC) is the18th most common cancer worldwide and the 8th most common in women. The aim of this study was to diagnose the potential importance of, as well as novel genes linked with, EOC and to provide valid biological information [...] Read more.
Epithelial ovarian cancer (EOC) is the18th most common cancer worldwide and the 8th most common in women. The aim of this study was to diagnose the potential importance of, as well as novel genes linked with, EOC and to provide valid biological information for further research. The gene expression profiles of E-MTAB-3706 which contained four high-grade ovarian epithelial cancer samples, four normal fallopian tube samples and four normal ovarian epithelium samples were downloaded from the ArrayExpress database. Pathway enrichment and Gene Ontology (GO) enrichment analysis of differentially expressed genes (DEGs) were performed, and protein-protein interaction (PPI) network, microRNA-target gene regulatory network and TFs (transcription factors) -target gene regulatory network for up- and down-regulated were analyzed using Cytoscape. In total, 552 DEGs were found, including 276 up-regulated and 276 down-regulated DEGs. Pathway enrichment analysis demonstrated that most DEGs were significantly enriched in chemical carcinogenesis, urea cycle, cell adhesion molecules and creatine biosynthesis. GO enrichment analysis showed that most DEGs were significantly enriched in translation, nucleosome, extracellular matrix organization and extracellular matrix. From protein-protein interaction network (PPI) analysis, modules, microRNA-target gene regulatory network and TFs-target gene regulatory network for up- and down-regulated, and the top hub genes such as E2F4, SRPK2, A2M, CDH1, MAP1LC3A, UCHL1, HLA-C (major histocompatibility complex, class I, C), VAT1, ECM1 and SNRPN (small nuclear ribonucleoprotein polypeptide N) were associated in pathogenesis of EOC. The high expression levels of the hub genes such as CEBPD (CCAAT enhancer binding protein delta) and MID2 in stages 3 and 4 were validated in the TCGA (The Cancer Genome Atlas) database. CEBPD andMID2 were associated with the worst overall survival rates in EOC. In conclusion, the current study diagnosed DEGs between normal and EOC samples, which could improve our understanding of the molecular mechanisms in the progression of EOC. These new key biomarkers might be used as therapeutic targets for EOC. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Show Figures

Figure 1

Review

Jump to: Research, Other

Open AccessReview
Clinical Utility of Preoperative Assessment in Ovarian Cancer Cytoreduction
Diagnostics 2020, 10(8), 568; https://doi.org/10.3390/diagnostics10080568 - 07 Aug 2020
Abstract
Ovarian cancer is the deadliest gynecologic cancer, in part due to late presentation. Many women have vague early symptoms and present with disseminated disease. Cytoreductive surgery can be extensive, involving multiple organ systems. Novel therapies and recent clinical trials have provided evidence that, [...] Read more.
Ovarian cancer is the deadliest gynecologic cancer, in part due to late presentation. Many women have vague early symptoms and present with disseminated disease. Cytoreductive surgery can be extensive, involving multiple organ systems. Novel therapies and recent clinical trials have provided evidence that, compared to primary cytoreduction, neoadjuvant chemotherapy has equivalent survival outcomes with less morbidity. There is increasing need for validated tools and mechanisms for clinicians to determine the optimal management of ovarian cancer patients. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Show Figures

Figure 1

Open AccessReview
Immune Checkpoint Inhibitors in Epithelial Ovarian Cancer: An Overview on Efficacy and Future Perspectives
Diagnostics 2020, 10(3), 146; https://doi.org/10.3390/diagnostics10030146 - 07 Mar 2020
Cited by 5
Abstract
Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological cancers. Despite improvements in medical treatments, the prognosis for EOC remains poor, and there is an urgent need for new therapeutic strategies. Immune checkpoint inhibitors (CPIs) have dramatically improved survival of [...] Read more.
Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological cancers. Despite improvements in medical treatments, the prognosis for EOC remains poor, and there is an urgent need for new therapeutic strategies. Immune checkpoint inhibitors (CPIs) have dramatically improved survival of several cancers and are under evaluation in OC. Unfortunately, CPIs have shown globally unsatisfactory results. The aim of this manuscript is to critically review the results from early-phase trials with CPIs in terms of safety and activity, discuss the possible reasons for disappointing results and the new therapeutic approaches to improve patient outcomes. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Open AccessReview
Screening and Prevention for High-Grade Serous Carcinoma of the Ovary Based on Carcinogenesis—Fallopian Tube- and Ovarian-Derived Tumors and Incessant Retrograde Bleeding
Diagnostics 2020, 10(2), 120; https://doi.org/10.3390/diagnostics10020120 - 22 Feb 2020
Cited by 2
Abstract
High-grade serous carcinoma (HGSC) is the most common and lethal subtype of ovarian carcinoma. Many HGSCs are now believed to originate in the fallopian tube epithelium; ovarian surface epithelium is another possible origin. Thus, current screening methods, i.e., ultrasonography and serum CA-125 measurements, [...] Read more.
High-grade serous carcinoma (HGSC) is the most common and lethal subtype of ovarian carcinoma. Many HGSCs are now believed to originate in the fallopian tube epithelium; ovarian surface epithelium is another possible origin. Thus, current screening methods, i.e., ultrasonography and serum CA-125 measurements, have a limitation in their early detection. Recently, circulating biomarkers, such as tumor DNA, autoantibody, and microRNA, have been investigated to detect HGSCs. As cancer cells in the fallopian tube flow into the endometrial cavity, the detection of exfoliated cells, tumor DNA, and proteome from samples obtained from the endometrial cavity or the cervix may be useful. The risk of ovarian serous carcinoma is affected by the use of oral contraceptive and menopausal hormone therapy (MHT). MHT regimens causing endometrial bleeding increase serous carcinoma risk, hence, incessant retrograde bleeding from the endometrial cavity into the Douglas pouch appears to play an important role in high-grade serous carcinogenesis. In this review, we provide an overview of current and novel screening methods and prevention approaches for ovarian and fallopian tube HGSC. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Open AccessReview
Serous Tubal Intraepithelial Carcinoma: A Concise Review for the Practicing Pathologist and Clinician
Diagnostics 2020, 10(2), 102; https://doi.org/10.3390/diagnostics10020102 - 13 Feb 2020
Abstract
Ovarian cancer is the deadliest gynecologic malignancy, accounting for more than 14,000 deaths each year. With no established way to prevent or screen for it, the vast majority of cases are diagnosed as International Federation of Gynecology and Obstetrics (FIGO) stage III or [...] Read more.
Ovarian cancer is the deadliest gynecologic malignancy, accounting for more than 14,000 deaths each year. With no established way to prevent or screen for it, the vast majority of cases are diagnosed as International Federation of Gynecology and Obstetrics (FIGO) stage III or higher. Individuals with germline BRCA mutations are at particularly high risk for epithelial ovarian cancer and have been the subject of many risk-reducing strategies. In the past ten years, studies looking at risk-reducing salpingo-oophorectomy (RRSO) in this population have uncovered an interesting association: up to 8% of women with BRCA1 or BRCA2 mutations who underwent RRSO had an associated serous tubal intraepithelial carcinoma (STIC). The importance of this finding is highlighted by the fact that up to 60% of ovarian cancer patients will also have an associated STIC. These studies have led to a paradigm shift that a subset of epithelial ovarian cancer originates not in the ovarian epithelium, but rather in the distal fallopian tube. In response to this, many providers have changed their practice by expanding the role of routine salpingectomy, hysterectomy, and sterilization procedures. The American College of Obstetricians and Gynecologists (ACOG) has acknowledged opportunistic salpingectomy as a safe strategy to reduce the risk of epithelial ovarian cancer in Committee Opinion #774. It is thus important for pathologists and clinicians to understand the definition of STIC; how it is diagnosed; and, most importantly, its clinical significance. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Show Figures

Figure 1

Open AccessReview
Ovarian Seromucinous Tumors: Pathogenesis, Morphologic Spectrum, and Clinical Issues
Diagnostics 2020, 10(2), 77; https://doi.org/10.3390/diagnostics10020077 - 31 Jan 2020
Cited by 4
Abstract
Ovarian seromucinous tumors were introduced in the 2014 World Health Organization (WHO) classification as one of the seven types of ovarian epithelial tumors. They are characterized by frequent association with endometriosis and bilaterality, microscopic appearance of papillary architecture, and admixture of a variety [...] Read more.
Ovarian seromucinous tumors were introduced in the 2014 World Health Organization (WHO) classification as one of the seven types of ovarian epithelial tumors. They are characterized by frequent association with endometriosis and bilaterality, microscopic appearance of papillary architecture, and admixture of a variety of müllerian-type epithelium. They are considered to be endometriosis-related ovarian neoplasms, along with endometrioid and clear cell tumors; recent molecular studies suggest this particular tumor is a variant of endometrioid tumor. Discrepancies in nomenclature, definition, and morphology of seromucinous tumors appear to be a source of confusion, for both clinicians and general surgicalpathologists. This review summarizes the clinicopathological features of benign, borderline, and malignant seromucinous tumors, as well as controversies regarding these tumors. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Show Figures

Figure 1

Open AccessReview
Mucinous Cancer of the Ovary: Overview and Current Status
Diagnostics 2020, 10(1), 52; https://doi.org/10.3390/diagnostics10010052 - 19 Jan 2020
Cited by 8
Abstract
Mucinous ovarian cancer (MOC) is a rare subtype of epithelial ovarian carcinoma (EOC). Whereas all EOC subtypes are addressed in the same way, MOC is a distinct entity. Appreciating the pathological features and genomic profile of MOC may result in the improvement in [...] Read more.
Mucinous ovarian cancer (MOC) is a rare subtype of epithelial ovarian carcinoma (EOC). Whereas all EOC subtypes are addressed in the same way, MOC is a distinct entity. Appreciating the pathological features and genomic profile of MOC may result in the improvement in management and, hence, the prognosis. Distinguishing primary MOC from metastatic mucinous carcinoma can be challenging but is essential. Early-stage MOC carries an excellent prognosis, with advanced disease having a poor outcome. Surgical management plays an essential role in the early stage and in metastatic disease. Chemotherapy is usually administered for stage II MOC and beyond. The standard gynecology protocol is frequently used, but gastrointestinal regimens have also been administered. As MOC is associated with multiple molecular alterations, targeted therapy could be the answer to treat this disease. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Show Figures

Figure 1

Open AccessReview
Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer
Diagnostics 2020, 10(1), 43; https://doi.org/10.3390/diagnostics10010043 - 14 Jan 2020
Cited by 5
Abstract
Hyperthermic intraperitoneal chemotherapy (HIPEC) in conjunction with cytoreductive surgery (CRS) holds promise as an adjunctive treatment strategy in malignancies affecting the peritoneal surface, effectively targeting remaining microscopic residual tumor. HIPEC increases concentrations of chemotherapy directly within the peritoneal cavity compared with the intravenous [...] Read more.
Hyperthermic intraperitoneal chemotherapy (HIPEC) in conjunction with cytoreductive surgery (CRS) holds promise as an adjunctive treatment strategy in malignancies affecting the peritoneal surface, effectively targeting remaining microscopic residual tumor. HIPEC increases concentrations of chemotherapy directly within the peritoneal cavity compared with the intravenous route and reduces the systemic side effects associated with prolonged adjuvant intraperitoneal exposure. Furthermore, hyperthermia increases tissue penetration and is synergistic with the therapeutic chemotherapy agents used. In ovarian cancer, evidence is building for its use in both primary and recurrent scenarios. In this review, we examine the history of HIPEC, the techniques used, and the available data guiding its use in primary and recurrent ovarian cancer. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Show Figures

Figure 1

Open AccessReview
Characteristics of in Vivo Model Systems for Ovarian Cancer Studies
Diagnostics 2019, 9(3), 120; https://doi.org/10.3390/diagnostics9030120 - 14 Sep 2019
Cited by 6
Abstract
An understanding of the molecular pathogenesis and heterogeneity of ovarian cancer holds promise for the development of early detection strategies and novel, efficient therapies. In this review, we discuss the advantages and limitations of animal models available for basic and preclinical studies. The [...] Read more.
An understanding of the molecular pathogenesis and heterogeneity of ovarian cancer holds promise for the development of early detection strategies and novel, efficient therapies. In this review, we discuss the advantages and limitations of animal models available for basic and preclinical studies. The fruit fly model is suitable mainly for basic research on cellular migration, invasiveness, adhesion, and the epithelial-to-mesenchymal transition. Higher-animal models allow to recapitulate the architecture and microenvironment of the tumor. We discuss a syngeneic mice model and the patient derived xenograft model (PDX), both useful for preclinical studies. Conditional knock-in and knock-out methodology allows to manipulate selected genes at a given time and in a certain tissue. Such models have built our knowledge about tumor-initiating genetic events and cell-of-origin of ovarian cancers; it has been shown that high-grade serous ovarian cancer may be initiated in both the ovarian surface and tubal epithelium. It is postulated that clawed frog models could be developed, enabling studies on tumor immunity and anticancer immune response. In laying hen, ovarian cancer develops spontaneously, which provides the opportunity to study the genetic, biochemical, and environmental risk factors, as well as tumor initiation, progression, and histological origin; this model can also be used for drug testing. The chick embryo chorioallantoic membrane is another attractive model and allows the study of drug response. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Show Figures

Graphical abstract

Open AccessReview
Combined Strategies with Poly (ADP-Ribose) Polymerase (PARP) Inhibitors for the Treatment of Ovarian Cancer: A Literature Review
Diagnostics 2019, 9(3), 87; https://doi.org/10.3390/diagnostics9030087 - 01 Aug 2019
Cited by 29
Abstract
Poly (ADP-ribose) polymerase (PARP) inhibitors are the first clinically approved drugs designed to exploit synthetic lethality, and were first introduced as a cancer-targeting strategy in 2005. They have led to a major change in the treatment of advanced ovarian cancer, and altered the [...] Read more.
Poly (ADP-ribose) polymerase (PARP) inhibitors are the first clinically approved drugs designed to exploit synthetic lethality, and were first introduced as a cancer-targeting strategy in 2005. They have led to a major change in the treatment of advanced ovarian cancer, and altered the natural history of a disease with extreme genetic complexity and defective DNA repair via homologous recombination (HR) pathway. Furthermore, additional mechanisms apart from breast related cancer antigens 1 and 2 (BRCA1/2) mutations can also result in HR pathway alterations and consequently lead to a clinical benefit from PARP inhibitors. Novel combinations of PARP inhibitors with other anticancer therapies are challenging, and better understanding of PARP biology, DNA repair mechanisms, and PARP inhibitor mechanisms of action is crucial. It seems that PARP inhibitor and biologic agent combinations appear well tolerated and clinically effective in both BRCA-mutated and wild-type cancers. They target differing aberrant and exploitable pathways in ovarian cancer, and may induce greater DNA damage and HR deficiency. The input of immunotherapy in ovarian cancer is based on the observation that immunosuppressive microenvironments can affect tumour growth, metastasis, and even treatment resistance. Several biologic agents have been studied in combination with PARP inhibitors, including inhibitors of vascular endothelial growth factor (VEGF; bevacizumab, cediranib), and PD-1 or PD-L1 (durvalumab, pembrolizumab, nivolumab), anti-CTLA4 monoclonal antibodies (tremelimumab), mTOR-(vistusertib), AKT-(capivasertib), and PI3K inhibitors (buparlisib, alpelisib), as well as MEK 1/2, and WEE1 inhibitors (selumetinib and adavosertib, respectively). Olaparib and veliparib have also been combined with chemotherapy with the rationale of disrupting base excision repair via PARP inhibition. Olaparib has been investigated with carboplatin and paclitaxel, whereas veliparib has been tested additionally in combination with temozolomide vs. pegylated liposomal doxorubicin, as well as with oral cyclophosphamide, and topoisomerase inhibitors. However, overlapping myelosuppression observed with PARP inhibitor and chemotherapy combinations requires further investigation with dose escalation studies. In this review, we discuss multiple clinical trials that are underway examining the antitumor activity of such combination strategies. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Open AccessReview
PARP Inhibitors in Ovarian Cancer: The Route to “Ithaca”
Diagnostics 2019, 9(2), 55; https://doi.org/10.3390/diagnostics9020055 - 18 May 2019
Cited by 19
Abstract
Poly (ADP-ribose) polymerase (PARP) inhibitors are a novel class of therapeutic agents that target tumors with deficiencies in the homologous recombination DNA repair pathway. Genomic instability characterizes high-grade serous ovarian cancer (HGSOC), with one half of all tumors displaying defects in the important [...] Read more.
Poly (ADP-ribose) polymerase (PARP) inhibitors are a novel class of therapeutic agents that target tumors with deficiencies in the homologous recombination DNA repair pathway. Genomic instability characterizes high-grade serous ovarian cancer (HGSOC), with one half of all tumors displaying defects in the important DNA repair pathway of homologous recombination. Early studies have shown significant efficacy for PARP inhibitors in patients with germline breast related cancer antigens 1 and 2 (BRCA1/2) mutations. It has also become evident that BRCA wild-type patients with other defects in the homologous recombination repair pathway benefit from this treatment. Companion homologous recombination deficiency (HRD) scores are being developed to guide the selection of patients that are most likely to benefit from PARP inhibition. The choice of which PARP inhibitor is mainly based upon the number of prior therapies and the presence of a BRCA mutation or HRD. The identification of patients most likely to benefit from PARP inhibitor therapy in view of HRD and other biomarker assessments is still challenging. The aim of this review is to describe the current evidence for PARP inhibitors in ovarian cancer, their mechanism of action, and the outstanding issues, including the rate of long-term toxicities and the evolution of resistance. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)

Other

Jump to: Research, Review

Open AccessViewpoint
Rethinking the Role of Radiation Therapy in the Management of Epithelial Ovarian Cancer
Diagnostics 2020, 10(4), 211; https://doi.org/10.3390/diagnostics10040211 - 11 Apr 2020
Abstract
Radiation has been relegated to a palliative role in the management of epithelial ovarian cancer (EOC). Contemporary radiation techniques, including intensity modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and image-guided radiation therapy, enable conformal treatment that controls local disease with minimal [...] Read more.
Radiation has been relegated to a palliative role in the management of epithelial ovarian cancer (EOC). Contemporary radiation techniques, including intensity modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and image-guided radiation therapy, enable conformal treatment that controls local disease with minimal morbidity. Recent studies from multiple institutions support the role of radiation in the ablative treatment of oligometastatic disease and control of locally recurrent and metastatic disease. Effective local treatment with radiation complements the role of systemic therapy in the management of EOC; reduces symptoms and disease burden, and may contribute to a prolonged drug free interval. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Back to TopTop