The additional prognostic value of morphometric nuclear arrangement and DNA-ploidy to other morphometric and stereologic features in endometrial hyperplasias

Earlier studies have shown that morphometric analysis of nuclear size and shape features and stereologic analysis of gland architecture in endometrial hyperplasia are useful to predict the risk of progression to cancer. A multivariate discriminatory D-score using these features has a higher sensitivity than qualitative microscopic characteristics (nuclear atypicality and glandular complexity) when an appropriate threshold is chosen. In the present study, the (additional) prognostic value of morphometric features related to the arrangement of nuclei in glands (distance of nuclear centroids to basal membrane, angle of longest nuclear axis with basal membrane) and DNA-ploidy (determined by flow cytometry) has been analyzed in 39 cases of endometrial hyperplasia, seven (18%) of which have progressed to cancer. Variation in stratification of nuclei has prognostic value, in contrast to DNA-ploidy. Multivariate analysis selects the outer surface density of the glands, mean distance, volume percentage of lumen and the coefficient of variation of nuclear axes as having separate and additional value. A multivariate rule called HYPER-score results from these features. With this score a high-risk (score value ≥0.20, nine cases, 78% progressed) and a low-risk group (score value <0.20, 30 cases, none progressed) can be discerned. The prognostic value, sensitivity and specificity of the hyper-score greatly exceeds that of any of the previously described prognostic factors in endometrial hyperplasias. An additional clinical advantage is that with the HYPER-score two groups (instead of four groups as with Kurman's method(1)) with a high sensitivity and specificity can be discerned. The morphometric and stereologic features agree well with the usual qualitative predictors but have much stronger prognostic value.

Download Full-text

Diagnostic and Prognostic Value of Circulating CircRNAs in Cancer

Frontiers in Medicine ◽

10.3389/fmed.2021.649383 ◽

2021 ◽

Vol 8 ◽

Author(s):

Mina Wang ◽

Feiyu Xie ◽

Jiaran Lin ◽

Yihan Zhao ◽

Qian Zhang ◽

...

Keyword(s):

Sensitivity And Specificity ◽

Prognostic Value ◽

Rna Binding ◽

Rna Binding Proteins ◽

High Sensitivity ◽

High Specificity ◽

Protein Translation ◽

Circular Rnas ◽

Protein Scaffolding ◽

Diagnostic And Prognostic Value

Cancer has been regarded as one of the leading causes of mortality worldwide. Diagnostic and prognostic biomarkers with high sensitivity and specificity for cancer play a crucial role in preventing or treating cancer. Circular RNAs (circRNAs), which hold great potential for the management of cancer patients due to their abundance, stable property, and high specificity in serum, plasma, and other body fluids, can be used as non-invasive and blood-based biomarkers in cancer diagnosis and prognosis. There are four types of circRNAs including exonic circRNAs (ecircRNA), intronic circRNAs, exon-intron circRNAs (EIciRNA), and intergenic circRNAs. CircRNAs can act as miRNA sponges, affect protein translation, interplay with RNA binding proteins, regulate protein recruitment, and modulate protein scaffolding and assembly. Therefore, the multifunctionalities of circRNAs make them ideal for detecting and predicting cancer. Indeed, circRNAs manifest high sensitivity and specificity in more than ten types of cancer. This review aims to consolidate the types and functions of circRNAs, as well as discuss the diagnostic and prognostic value of circulating circRNAs in cancer.

Download Full-text

CADM1, MAL, and miR124 Promoter Methylation as Biomarkers of Transforming Cervical Intrapithelial Lesions

International Journal of Molecular Sciences ◽

10.3390/ijms20092262 ◽

2019 ◽

Vol 20 (9) ◽

pp. 2262 ◽

Cited By ~ 3

Author(s):

Marta del Pino ◽

Adriana Sierra ◽

Lorena Marimon ◽

Cristina Martí Delgado ◽

Adriano Rodriguez-Trujillo ◽

...

Keyword(s):

Sensitivity And Specificity ◽

Promoter Methylation ◽

Methylation Status ◽

High Sensitivity ◽

Control Group ◽

Low Grade ◽

Papilloma Virus ◽

Specific Pcr ◽

Risk Of Progression ◽

Intraepithelial Lesions

Background: Squamous intraepithelial lesions/cervical intraepithelial neoplasias (SIL/CIN) are high-risk human papilloma virus (hrHPV)-related lesions which are considered as high grade (HSIL/CIN2-3) or low grade (LSIL/CIN1) lesions according to their risk of progression to cervical cancer (CC). Most HSIL/CIN2-3 are considered as transforming hrHPV infections, so truly CC precursors, although some clear spontaneously. hrHPV testing has a high sensitivity for the detection of HSIL/CIN2-3 but a relatively low specificity for identifying transforming lesions. We aimed to determine whether the combination of CADM1, MAL and miR124 promoter methylation status assessed in histological samples can be used as a biomarker in the identification of transforming HSIL/CIN lesions. Design: 131 cervical biopsies, including 8 cases with no lesion and a negative hrHPV test result (control group), 19 low-grade (L)SIL/CIN1, 30 HSIL/CIN2, 60 HSIL/CIN3, and 14 CC were prospectively collected. hrHPV was detected and genotyped using the polymerase chain reaction (PCR)-based technique SPF10 HPV LIPA. A multiplex quantitative methylation-specific PCR (qMSP) was used to identify the methylation status of the CADM1, MAL, and miR124 promoter genes. Results: Significantly higher methylation levels of CADM1, MAL and miR-124 were found in HSIL/CIN2-3 and CC compared with normal and LSIL lesions. DNA methylation of at least one gene was detected in 12.5% (1/8) of normal samples, 31.5% (6/19) of LSIL/CIN1, 83.3% (25/30) of HSIL/CIN2, 81.6% (49/60) of HSIL/CIN3 and 100% (14/14) of CC (p < 0.001). The sensitivity and specificity for HSIL/CIN2-3 and CC of having at least one methylated gene were 84.6% and 74.0%, respectively. The sensitivity and specificity of the combination of at least one methylated gene and a positive hrHPV test were 80.7% and 85.1% for HSIL/CIN2-3 and CC, respectively. Conclusions: The methylation rate of CADM1, MAL and miR124 increases with the severity of the lesion. Further research is warranted to evaluate the usefulness of these biomarkers for the identification of transforming HSIL/CIN.

Download Full-text

Detector-C: A Blood-based IVD with High Sensitivity and Specificity for Early Detection and Screening of Colorectal Cancer

Zeitschrift für Gastroenterologie ◽

10.1055/s-0030-1263628 ◽

2010 ◽

Vol 48 (08) ◽

Author(s):

A Rosenthal ◽

H Köppen ◽

R Musikowski ◽

R Schwanitz ◽

J Behrendt ◽

...

Keyword(s):

Colorectal Cancer ◽

Early Detection ◽

Sensitivity And Specificity ◽

High Sensitivity

Download Full-text

Trends in Diagnosis for Active Tuberculosis Using Nanomaterials

Current Medicinal Chemistry ◽

10.2174/0929867325666180912105617 ◽

2019 ◽

Vol 26 (11) ◽

pp. 1946-1959 ◽

Cited By ~ 3

Author(s):

Le Minh Tu Phan ◽

Lemma Teshome Tufa ◽

Hwa-Jung Kim ◽

Jaebeom Lee ◽

Tae Jung Park

Keyword(s):

Sensitivity And Specificity ◽

High Efficiency ◽

Point Of Care ◽

High Sensitivity ◽

Signs And Symptoms ◽

Diagnostic Methods ◽

Advantages And Disadvantages ◽

Treatment And Prevention ◽

Clinical Tools ◽

Diagnostic Applications

Background:Tuberculosis (TB), one of the leading causes of death worldwide, is difficult to diagnose based only on signs and symptoms. Methods for TB detection are continuously being researched to design novel effective clinical tools for the diagnosis of TB.Objective:This article reviews the methods to diagnose TB at the latent and active stages and to recognize prospective TB diagnostic methods based on nanomaterials.Methods:The current methods for TB diagnosis were reviewed by evaluating their advantages and disadvantages. Furthermore, the trends in TB detection using nanomaterials were discussed regarding their performance capacity for clinical diagnostic applications.Results:Current methods such as microscopy, culture, and tuberculin skin test are still being employed to diagnose TB, however, a highly sensitive point of care tool without false results is still needed. The utilization of nanomaterials to detect the specific TB biomarkers with high sensitivity and specificity can provide a possible strategy to rapidly diagnose TB. Although it is challenging for nanodiagnostic platforms to be assessed in clinical trials, active TB diagnosis using nanomaterials is highly expected to achieve clinical significance for regular application. In addition, aspects and future directions in developing the high-efficiency tools to diagnose active TB using advanced nanomaterials are expounded.Conclusion:This review suggests that nanomaterials have high potential as rapid, costeffective tools to enhance the diagnostic sensitivity and specificity for the accurate diagnosis, treatment, and prevention of TB. Hence, portable nanobiosensors can be alternative effective tests to be exploited globally after clinical trial execution.

Download Full-text

Value of Coronary Calcium Scoring in Symptomatic and Asymptomatic Coronary Artery Disease Patients

Current Medical Imaging Formerly Current Medical Imaging Reviews ◽

10.2174/1573405616666201023142030 ◽

2020 ◽

Vol 16 ◽

Author(s):

Hala T. Salem ◽

Eman A.S. Sabek

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Sensitivity And Specificity ◽

High Sensitivity ◽

Coronary Calcium ◽

Risk Estimate ◽

Calcium Scoring ◽

Coronary Calcium Scoring ◽

Framingham Risk ◽

Artery Disease

Aim and Objective: To estimate the relationship between Coronary Calcium Scoring (CCS)and presence of different degrees of obstructive coronary artery disease (CAD) to avoid unnecessary examinations and hence unnecessary radiation exposure and contrast injection. Background: Coronary Calcium Scoring (CCS) is a test uses x-ray equipment to produce pictures of the coronary arteries to determine the degree of its narrowing by the build-up of calcified plaques. Despite the lack of definitive data linking ionizing radiation with cancer, the American Heart Association supports widely that practitioners of Computed tomography Coronary Angiography (CTCA) should keep “patient radiation doses as low as reasonably achievable but consistent with obtaining the desired medical information”. Methods: Data obtained from 275 CTCA examinations were reviewed. Radiation effective doses were estimated for both CCS and CTCA, measures to keep it as low as possible were presented, CCS and Framingham risk estimate were compared to the final results of CTCA to detect sensitivity and specificity of each one in detecting obstructive lesions. Results: CCS is a strong discriminator for obstructive CAD and can with high sensitivity and specificity and correlates well with the degree of obstruction even more than Framingham risk estimate which has high sensitivity and low specificity. Conclusion: CCS helps reducing the effective radiation dose if properly evaluated to skip unnecessary CTCA if obstructive lesions was unlikely, and as a test does not use contrast material, harmful effect on the kidney will be avoided as most of coronary atherosclerotic patients have renal problems.

Download Full-text

Blood-Based Detection of Colorectal Cancer Using Cancer-Specific DNA Methylation Markers

Diagnostics ◽

10.3390/diagnostics11010051 ◽

2020 ◽

Vol 11 (1) ◽

pp. 51

Author(s):

Nam-Yun Cho ◽

Ji-Won Park ◽

Xianyu Wen ◽

Yun-Joo Shin ◽

Jun-Kyu Kang ◽

...

Keyword(s):

Colorectal Cancer ◽

Dna Methylation ◽

Sensitivity And Specificity ◽

Stage Iv ◽

High Sensitivity ◽

Liquid Biopsies ◽

Blood Leukocytes ◽

Marker Panel ◽

A Genome ◽

Methylight Assay

Cancer tissues have characteristic DNA methylation profiles compared with their corresponding normal tissues that can be utilized for cancer diagnosis with liquid biopsy. Using a genome-scale DNA methylation approach, we sought to identify a panel of DNA methylation markers specific for cell-free DNA (cfDNA) from patients with colorectal cancer (CRC). By comparing DNA methylomes between CRC and normal mucosal tissues or blood leukocytes, we identified eight cancer-specific methylated loci (ADGRB1, ANKRD13, FAM123A, GLI3, PCDHG, PPP1R16B, SLIT3, and TMEM90B) and developed a five-marker panel (FAM123A, GLI3, PPP1R16B, SLIT3, and TMEM90B) that detected CRC in liquid biopsies with a high sensitivity and specificity with a droplet digital MethyLight assay. In a set of cfDNA samples from CRC patients (n = 117) and healthy volunteers (n = 60), a panel of five markers on the platform of the droplet digital MethyLight assay detected stages I–III and stage IV CRCs with sensitivities of 45.9% and 95.7%, respectively, and a specificity of 95.0%. The number of detected markers was correlated with the cancer stage, perineural invasion, lymphatic emboli, and venous invasion. Our five-marker panel with the droplet digital MethyLight assay showed a high sensitivity and specificity for the detection of CRC with cfDNA samples from patients with metastatic CRC.

Download Full-text