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Screening and Tests for Gynecologic Cancer
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Screening and Tests for Gynecologic Cancer

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Obstetrics & Gynecology".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 18067

Special Issue Editor

Prof. Dr. Satoru Kyo

E-Mail Website
Guest Editor
Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo, Japan
Interests: gynecologic cancer; gene therapy; cervical cancer; microRNA; ovarian cancer; adenovirus; HPV

Special Issue Information

Dear Colleagues,

Diagnostics of gynecologic cancers has stepped into a new phase via recent advances in molecular biology, which provide us with a broad spectrum of diagnostic information. Specific gene mutations and gene expression signatures in each cancer type have been identified through molecular technologies, including next-generation sequencing and microarray analyses, which can be helpful for the diagnosis as well as the decision of treatment strategy. Liquid biopsy techniques are becoming a special tool for the early diagnosis of gynecologic cancers, especially with miRNAs or cancer-specific replication viruses. Another topic of the screening of gynecologic cancers lies in familial and hereditary cancers, including hereditary breast and ovarian cancer and Lynch syndrome. It is an important issue to address how effectively these patients can be screened and diagnosed using genetic markers, such as the status of BRCA or microsatellite instability (MSI). In cervical cancers, human papillomavirus (HPV) testing has continued to be a hot topic, but how to use HPV testing for the best screening is yet to be resolved. Furthermore, there are diagnostic problems on HPV-negative cancer, such as some types of cervical adenocarcinoma. In this Special Issue, the current status of novel technologies for the screening and diagnosis of gynecologic cancers will be introduced and how to use them or fuse them to conventional methods will be discussed.

Prof. Dr. Satoru Kyo
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 submissions that pass pre-check are 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. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly 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 2600 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

  • Gynecologic cancer
  • Genomic medicine
  • Liquid biopsy
  • microRNA
  • Familial and hereditary cancer
  • BRCA
  • MSI
  • HPV test

Published Papers (7 papers)

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Research

Jump to: Review

16 pages, 702 KiB  
Article
Betaglycan Gene (TGFBR3) Polymorphism Is Associated with Increased Risk of Endometrial Cancer
by Piotr K. Zakrzewski, Ewa Forma, Adam I. Cygankiewicz, Magdalena Bryś, Katarzyna Wójcik-Krowiranda, Andrzej Bieńkiewicz, Andrzej Semczuk and Wanda M. Krajewska
J. Clin. Med. 2020, 9(10), 3082; https://doi.org/10.3390/jcm9103082 - 24 Sep 2020
Cited by 5 | Viewed by 2359
Abstract
We investigated single nucleotide polymorphism (SNP) of the betaglycan gene (TGFBR3) encoding the TGFβ co-receptor in endometrial cancer (EC) and its association with betaglycan expression. The study group included 153 women diagnosed with EC and 248 cancer-free controls. SNP genotyping and [...] Read more.
We investigated single nucleotide polymorphism (SNP) of the betaglycan gene (TGFBR3) encoding the TGFβ co-receptor in endometrial cancer (EC) and its association with betaglycan expression. The study group included 153 women diagnosed with EC and 248 cancer-free controls. SNP genotyping and gene expression were analyzed using TaqMan probes. Three out of the eight SNPs tested, i.e., rs12566180 (CT; OR = 2.22; 95% CI = 1.15–4.30; p = 0.0177), rs6680463 (GC; OR = 2.34; 95% CI = 1.20–4.53; p = 0.0120) and rs2296621 (TT; OR = 6.40; 95% CI = 1.18–34.84; p = 0.0317) were found to be significantly associated with increased risk of EC (adjusted to age, body mass index, menarche and parity). Among the analyzed SNPs, only rs2296621 demonstrated the impact on the increased cancer aggressiveness evaluated by the WHO grading system (G3 vs. G1/2, GT—OR = 4.04; 95% CI = 1.56–10.51; p = 0.0026; T—OR = 2.38; 95% CI = 1.16–4.85; p = 0.0151). Linkage disequilibrium (LD) analysis revealed high LD (r2 ≥ 0.8) in two haploblocks, constructed by rs2770186/rs12141128 and rs12566180/rs6680463, respectively. In the case of C/C haplotype (OR = 4.82; 95% CI = 1.54–15.07; p = 0.0116—Bonferroni corrected) and T/G haplotype (OR = 3.25; 95% CI = 1.29–8.15; p = 0.0328—Bonferroni corrected) in haploblock rs12566180/rs6680463, significantly higher frequency was observed in patients with EC as compared to the control group. The genotype-phenotype studies showed that SNPs of the TGFBR3 gene associated with an increased risk of EC, i.e., rs12566180 and rs2296621 may affect betaglycan expression at the transcriptomic level (rs12566180—CC vs. TT, p < 0.01; rs2296621—GG vs. TT, p < 0.001, GT vs. TT, p < 0.05). Functional consequences of evaluated TGFBR3 gene SNPs were supported by RegulomeDB search. In conclusion, polymorphism of the TGFBR3 gene may be associated with an increased EC occurrence, as well as may be the molecular mechanism responsible for observed betaglycan down-regulation in EC patients. Full article
(This article belongs to the Special Issue Screening and Tests for Gynecologic Cancer)
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13 pages, 1115 KiB  
Article
The Prognostic Model of Pre-Treatment Complete Blood Count (CBC) for Recurrence in Early Cervical Cancer
by Joseph J. Noh, Myong Cheol Lim, Moon-Hong Kim, Yun Hwan Kim, Eun Seop Song, Seok Ju Seong, Dong Hoon Suh, Jong-Min Lee, Chulmin Lee and Chel Hun Choi
J. Clin. Med. 2020, 9(9), 2960; https://doi.org/10.3390/jcm9092960 - 13 Sep 2020
Cited by 3 | Viewed by 2455
Abstract
The aim of the present study was to investigate the prognostic role of the pre-treatment complete blood count (CBC) profile as a predictive marker of survival, recurrence, and death in early stage squamous cell carcinoma and adenocarcinoma of the cervix. The pre-treatment CBC [...] Read more.
The aim of the present study was to investigate the prognostic role of the pre-treatment complete blood count (CBC) profile as a predictive marker of survival, recurrence, and death in early stage squamous cell carcinoma and adenocarcinoma of the cervix. The pre-treatment CBC profiles of the patients from nine tertiary medical centers in South Korea who were treated surgically for early stage cervical cancer were reviewed. Statistical models by the Akaike’s information criterion (AIC) were developed using CBC profiles to calculate individuals’ risk scores for clinical outcomes. A total of 1443 patients were included in the study and the median follow-up was 63.7 months with a range of 3–183 months. Univariate analyses identified the components of CBC that were significantly related to clinical outcomes including white blood cell (WBC), hemoglobin, neutrophil, and platelet levels. The models developed using CBC profiles and the conventional clinical predictive factors provided individuals’ risk scores that were significantly better in predicting clinical outcomes than the models using the conventional clinical predictive factors alone. Pre-treatment CBC profiles including WBC, hemoglobin, neutrophil, lymphocyte, and platelet levels were found to be a potential biomarker for survival prognosis in early cervical cancer. Full article
(This article belongs to the Special Issue Screening and Tests for Gynecologic Cancer)
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13 pages, 485 KiB  
Article
Preoperative Neutrophil-to-Lymphocyte Ratio as a Prognostic Factor in Uterine Sarcoma
by Min Jin Jeong, Jung Hyun Park, Soo Young Hur, Chan Joo Kim, Hae Seong Nam and Yong Seok Lee
J. Clin. Med. 2020, 9(9), 2898; https://doi.org/10.3390/jcm9092898 - 8 Sep 2020
Cited by 13 | Viewed by 2213
Abstract
Background: Recent studies have demonstrated that the tumor microenvironment, known to be influenced by inflammatory cells, plays a crucial role in cancer progression and clinical outcome of patients. The objective of the present study was to investigate prognostic values of preoperative neutrophil-to-lymphocyte ratio [...] Read more.
Background: Recent studies have demonstrated that the tumor microenvironment, known to be influenced by inflammatory cells, plays a crucial role in cancer progression and clinical outcome of patients. The objective of the present study was to investigate prognostic values of preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for disease-free survival (DFS) and overall survival (OS) of uterine sarcoma patients. Methods: Ninety-nine patients with uterine sarcoma treated in eight multicenter institutions over the last 20 years were retrospectively analyzed. Curves of DFS and OS were calculated using the Kaplan–Meier method, and univariate and multivariate analyses of various prognostic factors were performed using a Cox proportional hazard regression model. Results: High NLR was significantly associated with worse DFS (p = 0.007) and OS (p = 0.039). Advanced stage (p = 0.017) and high mitotic index (p = 0.036) retained their prognostic significance for DFS. Other clinical variables, including PLR, CA125, and lactate dehydrogenase (LDH) failed to show significant impact. Conclusions: Our findings showed that an elevated preoperative NLR was associated with poor clinical outcome in uterine sarcoma patients. Our results suggest that high NLR in early-stage uterine sarcoma patients might indicate that such patients need more intensive treatments. Full article
(This article belongs to the Special Issue Screening and Tests for Gynecologic Cancer)
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14 pages, 1338 KiB  
Article
Nomogram Predicting the Likelihood of Parametrial Involvement in Early-Stage Cervical Cancer: Avoiding Unjustified Radical Hysterectomies
by Louise Benoit, Vincent Balaya, Benedetta Guani, Arnaud Bresset, Laurent Magaud, Helene Bonsang-Kitzis, Charlotte Ngô, Patrice Mathevet and Fabrice Lécuru
J. Clin. Med. 2020, 9(7), 2121; https://doi.org/10.3390/jcm9072121 - 5 Jul 2020
Cited by 11 | Viewed by 2757
Abstract
Background: We aimed to establish a tool predicting parametrial involvement (PI) in patients with early-stage cervical cancer and select a sub-group of patients who would most benefit from a less radical surgery. Methods: We retrospectively reviewed patients from two prospective multicentric databases—SENTICOL I [...] Read more.
Background: We aimed to establish a tool predicting parametrial involvement (PI) in patients with early-stage cervical cancer and select a sub-group of patients who would most benefit from a less radical surgery. Methods: We retrospectively reviewed patients from two prospective multicentric databases—SENTICOL I and II—from 2005 to 2012. Patients with early-stage cervical cancer (FIGO 2018 IA with lympho-vascular involvement to IIA1), undergoing radical surgery (hysterectomy or trachelectomy) with bilateral sentinel lymph node (SLN) mapping with no metastatic node or PI on pre-operative imaging, were included. Results: In total, 5.2% patients (11/211) presented a histologic PI. After univariate analysis, SLN status, lympho-vascular space invasion, deep stromal invasion and tumor size were significantly associated with PI and were included in our nomogram. Our predictive model had an AUC of 0.92 (IC95% = 0.86–0.98) and presented a good calibration. A low risk group, defined according to the optimal sensitivity and specificity, presented a predicted probability of PI of 2%. Conclusion: Patients could benefit from a two-step approach. Final surgery (i.e. radical surgery and/or lymphadenectomy) would depend on the SLN status and the probability PI calculated after an initial conization with bilateral SLN mapping. Full article
(This article belongs to the Special Issue Screening and Tests for Gynecologic Cancer)
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11 pages, 1098 KiB  
Article
Improving the Prognostic Performance of SUVmax in 18F-Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography Using Tumor-to-Liver and Tumor-to-Blood Standard Uptake Ratio for Locally Advanced Cervical Cancer Treated with Concurrent Chemoradiotherapy
by Gun Oh Chong, Shin Young Jeong, Yoon Hee Lee, Shin-Hyung Park, Hyun Jung Lee, Sang-Woo Lee, Dae Gy Hong and Yoon Soon Lee
J. Clin. Med. 2020, 9(6), 1878; https://doi.org/10.3390/jcm9061878 - 16 Jun 2020
Cited by 2 | Viewed by 1832
Abstract
Objective: We sought to evaluate whether the 18F-fluorodeoxyglucose uptake normalization of the primary tumor to both the liver and blood pool and lymph nodes to both the liver and blood pool can enhance the discrimination for prognosis prediction in patients with cervical [...] Read more.
Objective: We sought to evaluate whether the 18F-fluorodeoxyglucose uptake normalization of the primary tumor to both the liver and blood pool and lymph nodes to both the liver and blood pool can enhance the discrimination for prognosis prediction in patients with cervical cancer. Methods: A total of 156 patients with cervical cancer (International Federation of Gynecology and Obstetrics stages IIB–IV) treated with concurrent chemoradiotherapy (CCRT) were enrolled. The maximum standardized uptake value (SUVmax) of tumor (tSUVmax) and the lymph node (nSUVmax) divided by the SUVmean of the liver (tumor-to-liver ratio (TLR) and node-to-liver (NLR)) and blood pool (tumor-to-blood ratio (TBR) and node-to-blood ratio (NBR)) were investigated. Univariate and multivariate analyses of disease-free survival (DFS) and overall survival (OS) were performed using clinical and metabolic parameters. A receiver operating characteristic curve analysis was performed to compare the accuracy of the metabolic parameters. Results: The multivariate analysis revealed that NLR (hazard ratio ((HR): 3.54; 95% confidence interval (CI): 1.53–8.19; p = 0.0032) and NBR (HR: 3.38; 95% CI: 1.02–11.19; p = 0.0457)) were independent prognostic factors for DFS, while TLR (HR: 4.16; 95% CI: 1.19–14.50; p = 0.0252), TBR (HR: 3.01; 95% CI: 1.04–8.70; p = 0.0415), NLR (HR: 4.84; 95% CI: 1.58–14.81; p = 0.0057), and NBR (HR: 6.87; 95% CI: 1.55–30.54; p = 0.0113) were significant prognostic factors for OS. The normalization of tSUVmax to the liver or blood pool enhanced the discrimination for prediction of recurrence (tSUVmax vs. TLR; p = 0.0056 and tSUVmax vs. TBR; p = 0.0099) and death (tSUVmax vs. TLR; p < 0.0001 and tSUVmax vs. TBR; p = 0.0001). Conclusions: The normalization of tSUVmax was an independent prognostic factor and improved the discrimination for the prediction of tumor recurrence and death in patients with locally advanced cervical cancer treated with CCRT. Full article
(This article belongs to the Special Issue Screening and Tests for Gynecologic Cancer)
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Review

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16 pages, 793 KiB  
Review
A Novel Liquid Biopsy Strategy to Detect Small Amounts of Cancer Cells Using Cancer-Specific Replication Adenoviruses
by Masahiro Takakura, Emi Takata and Toshiyuki Sasagawa
J. Clin. Med. 2020, 9(12), 4044; https://doi.org/10.3390/jcm9124044 - 14 Dec 2020
Cited by 1 | Viewed by 2329
Abstract
Circulating tumor cells (CTCs) are a promising source of clinical and biological cancer information and can be a material for liquid biopsy. However, detecting and capturing these cells remains a challenge. Various biological factors (e.g., cell surface proteins, cell size, deformability, or dielectrophoresis) [...] Read more.
Circulating tumor cells (CTCs) are a promising source of clinical and biological cancer information and can be a material for liquid biopsy. However, detecting and capturing these cells remains a challenge. Various biological factors (e.g., cell surface proteins, cell size, deformability, or dielectrophoresis) have been applied to detect CTCs. Cancer cells dramatically change their characteristics during tumorigenesis and metastasis. Hence, defining a cell as malignant using such a parameter is difficult. Moreover, immortality is an essential characteristic of cancer cells. Telomerase elongates telomeres and plays a critical role in cellular immortality and is specifically activated in cancer cells. Thus, the activation of telomerase can be a good fingerprint for cancer cells. Telomerase cannot be recognized by antibodies in living cells because it is a nuclear enzyme. Therefore, telomerase-specific replication adenovirus, which expresses the green fluorescent protein, has been applied to detect CTCs. This review explores the overview of this novel technology and its application in gynecological cancers. Full article
(This article belongs to the Special Issue Screening and Tests for Gynecologic Cancer)
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24 pages, 550 KiB  
Review
MicroRNA-Based Fingerprinting of Cervical Lesions and Cancer
by Justyna Pisarska and Katarzyna Baldy-Chudzik
J. Clin. Med. 2020, 9(11), 3668; https://doi.org/10.3390/jcm9113668 - 15 Nov 2020
Cited by 16 | Viewed by 3246
Abstract
The regulatory functions of microRNA (miRNA) are involved in all processes contributing to carcinogenesis and response to viral infections. Cervical cancer in most cases is caused by the persistence of high-risk human papillomavirus (HR-HPV) infection. While oncogenic human papillomaviruses induce aberrant expression of [...] Read more.
The regulatory functions of microRNA (miRNA) are involved in all processes contributing to carcinogenesis and response to viral infections. Cervical cancer in most cases is caused by the persistence of high-risk human papillomavirus (HR-HPV) infection. While oncogenic human papillomaviruses induce aberrant expression of many cellular miRNAs, this dysregulation could be harnessed as a marker in early diagnosis of HR-HPV infection, cervical squamous intraepithelial lesions, and cancer. In recent years, growing data indicate that miRNAs show specific patterns at various stages of cervical pathology. The aim of this review is to systematize current reports on miRNA capacity that can be utilized in personalized diagnostics of cervical precancerous and cancerous lesions. The analysis of the resources available in online databases (National Center for Biotechnology Information—NCBI, PubMed, ScienceDirect, Scopus) was performed. To date, no standardized diagnostic algorithm using the miRNA pattern in cervical pathology has been defined. However, the high sensitivity and specificity of the reported assays gives hope for the development of non-invasive diagnostic tests that take into account the heterogeneity of tumor-related changes. Due to this variability resulting in difficult to predict clinical outcomes, precise molecular tools are needed to improve the diagnostic and therapeutic process. Full article
(This article belongs to the Special Issue Screening and Tests for Gynecologic Cancer)
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