scholarly journals CD10 and Das1: A Biomarker Study Using Immunohistochemistry to Subtype Gastric Intestinal Metaplasia

2021 ◽  
Author(s):  
Athanasios Koulis ◽  
Natasha Costanzo ◽  
Catherine Mitchell ◽  
Stephen Lade ◽  
David Goode ◽  
...  
Keyword(s):  
Intestinal Metaplasia ◽  
High Sensitivity ◽  
High Specificity ◽  
Expression Data ◽  
Gastric Intestinal Metaplasia ◽  
Whitney Test ◽  
Mann Whitney Test ◽  
Risk Of Progression ◽  
Low Sensitivity ◽  
Digital Quantification

Abstract Background: Intestinal metaplasia (IM) is considered a key pivot point in the Correa model of gastric cancer (GC). It is histologically subtyped into the complete and incomplete subtypes, the latter being associated with a greater risk of progression. However, the clinical utility of IM subtyping remains unclear, partially due to the absence of reliable defining biomarkers.Methods: Based on gene expression data and existing literature, we selected CD10 and Das1 as candidate biomarkers to distinguish complete and incomplete IM glands in tissues from patients without GC (IM-GC) and patients with GC (IM+GC). Immunohistochemical staining of individually subtyped IM glands was scored after blinding by two researchers using tissue belonging to both IM-GC and IM+GC patients. Whole tissue Das1 staining was further assessed using digital image quantification (cellSens Dimension, Olympus).Results: Across both cohorts CD10 stained the IM brush border and was shown to have a high sensitivity (87.5% and 94.9% in IM-GC and IM+GC patients respectively) and specificity (100.0% and 96.7% respectively) with an overall AUROC of 0.944 for complete IM glands. By contrast Das1 stained mainly goblet cells and the apical membrane of epithelial cells, mostly of incomplete IM glands with a low sensitivity (28.6% and 29.3% in IM-GC and IM+GC patients respectively) but high specificity (98.3% and 85.1% respectively) and an overall AUROC of 0.603 for incomplete IM glands. A combined logistic regression model showed a significant increase in AUROC for detecting complete IM glands (0.955 vs 0.970). Whole tissue digital quantification of Das1 staining showed a significant association with incomplete IM compared to complete IM, both in IM-GC and in IM+GC patients (p=0.016 and p=0.009 respectively, Mann-Whitney test and unpaired t test used). Additionally, complete IM in IM+GC patients exhibited significantly more Das1 staining than in IM-GC patients (p=0.019, Mann-Whitney test). Conclusions: These findings suggest that CD10 is an outstanding biomarker for complete IM and Das1 may be useful as a secondary biomarker for IM glands at greater risk of progression irrespective of IM subtype. Overall, the clinical use of these biomarkers could lead to improved patient stratification and targeted surveillance.

scholarly journals Role of endoscopy in suspicion of atrophic gastritis with and without intestinal metaplasia in comparison to histopathology

2021 ◽  
Vol 84 (1) ◽  
pp. 9-17
Author(s):  
H Ibrahim ◽  
A Shams El-Deen ◽  
ZA Kasemy ◽  
M Saad ◽  
AA Sakr
Keyword(s):  
Atrophic Gastritis ◽  
Intestinal Metaplasia ◽  
Sensitivity And Specificity ◽  
Chronic Gastritis ◽  
Gastrointestinal Symptoms ◽  
High Sensitivity ◽  
High Specificity ◽  
Poor Correlation ◽  
Gastric Lesions ◽  
Low Sensitivity

Background and study aims : Atrophic gastritis (AG) and intestinal metaplasia (IM) are established premalignant gastric lesions. Many studies documented a poor correlation between esophagogastroduodenoscopy (EGD) and histopathological (HP) findings of precancerous gastric lesions. The aim was to bridge the gap between endoscopy and HP in detection of chronic gastritis, AG and IM. Patients and methods : a prospective single-center study involved 150 patients with endoscopic criteria of gastric lesions with upper gastrointestinal symptoms referred for upper GI endoscopy met the endoscopic criteria and classified according to HP of biopsies from targeted gastric lesions into chronic gastritis (GI), AG(GII) or IM(GIII). We correlated the endoscopic criteria of the 3 groups with the HP results. Results : (73males & 75 females) with ages ranged17-75 years and mean± SD was 41.96 ± 15.95. GI, GII &GIII were [42 patients (28%),82 patients (54.7%) and 26 patients (17.3%)], respectively. Diffuse gastric mottling was more common in GI (74.3%, P<0.001), visible submucosal vessels, gastric atrophy predominated in GII (75.6, 82.3 & 73.1% (P 0.005,0.4 & <0.01)), respectively. Whitish raised lesions were more specific in GIII (85.7%) (P<0.001). The sensitivity and specificity of endoscopic suspicion of chronic gastritis were (86&88% in GI), (87&85% in GII) and (54% &100% in GIII) (p-0.001). The logistic regression model for risk factors was χ2= 25.74 and 49.32, p < 0.001. Conclusion : Conventional endoscopy has high sensitivity and specificity for suspicion of chronic gastritis and AG, but low sensitivity and very high specificity for IM. Targeted biopsies may be valuable with image enhanced techniques.

Epstein-Barr Virus (EBV)-Encoded RNA: Automated In-Situ Hybridization (ISH) Compared with Manual ISH and Immunohistochemistry for Detection of EBV in Pediatric Lymphoproliferative Disorders

2009 ◽  
Vol 12 (3) ◽  
pp. 195-199 ◽  
Author(s):  
Naim K. Fanaian ◽  
Cynthia Cohen ◽  
Sandra Waldrop ◽  
Jennifer Wang ◽  
Bahig M. Shehata
Keyword(s):  
In Situ Hybridization ◽  
Predictive Value ◽  
Epstein Barr Virus ◽  
High Sensitivity ◽  
High Specificity ◽  
Lymphoproliferative Disorders ◽  
Barr Virus ◽  
Epstein Barr ◽  
Low Sensitivity

Detection of Epstein-Barr virus (EBV) may be achieved by various methods, including EBV-encoded RNA (EBER) in-situ hybridization (ISH) and immunohistochemistry (IHC) for latent membrane protein (LMP-1). We compared novel automated ISH and IHC techniques in pediatric lymphoproliferative disorders with results obtained by manual ISH. Thirty-seven pediatric cases previously studied by manual EBER ISH (including 18 EBER-positive, 15 EBER-negative, and 4 EBER-equivocal cases) were used for the study. Automated EBER ISH and automated LMP-1 IHC were performed using the BondMax autostainer and prediluted EBER probe and EBV cell surface 1 to 4 at 1:50 dilution, respectively. Results of each of the automated techniques for EBV detection were compared with results by manual EBER ISH. Compared with manual EBER ISH as the gold standard, automated ISH had a sensitivity and specificity of 94% and 69%, respectively, accuracy of 83%, positive predictive value (PPV) of 79%, and negative predictive value (NPV) of 90%. Automated IHC had a sensitivity of 44%, specificity of 93%, accuracy of 67%, PPV of 88%, and NPV of 59%. Automated ISH and IHC correlated significantly ( P < 0.045). Automated ISH is useful for diagnosis of EBV-related pediatric neoplasms, being easy to perform and interpret and requiring only the technologist's time to set up and having a high sensitivity and NPV. The automated IHC protocol is of too low sensitivity for routine use, although results show high specificity and PPV.

scholarly journals Validation of the French version of the McLean Screening Instrument for Adolescent Borderline Personality Disorder (MSI-BPD)

2020 ◽  
Author(s):  
Bojan Mirkovic ◽  
Mario Speranza ◽  
Lionel Cailhol ◽  
Julien-Daniel Guelfi ◽  
Fernando Perez-Diaz ◽  
...  
Keyword(s):  
Borderline Personality Disorder ◽  
Personality Disorder ◽  
Psychometric Properties ◽  
High Sensitivity ◽  
High Specificity ◽  
Structured Interview ◽  
Screening Instrument ◽  
Borderline Personality ◽  
French Version ◽  
Low Sensitivity

Abstract Background: The study examines the psychometric properties of the French version of the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD) created by M. Zanarini to screen borderline personality disorder in clinical and non-clinical populations.Method: In this multicentric longitudinal study from the European Network on Borderline Personality Disorder, a sample of 84 adolescent patients from five psychiatric centres and 85 matched controls without psychiatric comorbidity completed the MSI-BPD, French version, and were interviewed with the Structured Interview for DSM-IV Personality (SIDP-IV), in order to assess the presence or absence of borderline personality disorder.Results: The MSI-BPD showed excellent internal consistency (α = 0.87 [0.84;0.90]). Compared to the semi-structured reference interview (SIDP-IV), the MSI-BPD showed substantial congruent validity (AUC = 0.93, CI 95%: 0.90 - 0.97). The optimal cut-off point in the present study was 5 or more, as it had relatively high sensitivity (0.87) and specificity (0.85). In our sample, the cut-off point (7 or more) proposed by the original developers of the MSI-BPD showed high specificity (0.95) but low sensitivity (0.63).Conclusions: The French version of the MSI-BPD is now available, and its psychometric properties are satisfactory. The French version of the MSI-PBD can be used as a screening tool for borderline personality disorder, for clinical purposes or in research studies.

scholarly journals Sensitivity and specificity of loss of heterozygosity analysis for the classification of rare germline variants in BRCA1/2: results of the observational AGO-TR1 study (NCT02222883)

2020 ◽  
pp. jmedgenet-2020-107353
Author(s):  
Jan Hauke ◽  
Philipp Harter ◽  
Corinna Ernst ◽  
Alexander Burges ◽  
Sandra Schmidt ◽  
...  
Keyword(s):  
Loss Of Heterozygosity ◽  
Sensitivity And Specificity ◽  
False Negative ◽  
High Sensitivity ◽  
High Specificity ◽  
Germline Variants ◽  
Variants Of Unknown Significance ◽  
Link Type ◽  
Registration Number ◽  
Low Sensitivity

Variant-specific loss of heterozygosity (LOH) analyses may be useful to classify BRCA1/2 germline variants of unknown significance (VUS). The sensitivity and specificity of this approach, however, remains unknown. We performed comparative next-generation sequencing analyses of the BRCA1/2 genes using blood-derived and tumour-derived DNA of 488 patients with ovarian cancer enrolled in the observational AGO-TR1 trial (NCT02222883). Overall, 94 pathogenic, 90 benign and 24 VUS were identified in the germline. A significantly increased variant fraction (VF) of a germline variant in the tumour indicates loss of the wild-type allele; a decreased VF indicates loss of the variant allele. We demonstrate that significantly increased VFs predict pathogenicity with high sensitivity (0.84, 95% CI 0.77 to 0.91), poor specificity (0.63, 95% CI 0.53 to 0.73) and poor positive predictive value (PPV; 0.71, 95% CI 0.62 to 0.79). Significantly decreased VFs predict benignity with low sensitivity (0.26, 95% CI 0.17 to 0.35), high specificity (1.0, 95% CI 0.96 to 1.00) and PPV (1.0, 95% CI 0.85 to 1.00). Variant classification based on significantly increased VFs results in an unacceptable proportion of false-positive results. A significantly decreased VF in the tumour may be exploited as a reliable predictor for benignity, with no false-negative result observed. When applying the latter approach, VUS identified in four patients can now be considered benign. Trial registration numberNCT02222883.

scholarly journals Molecular markers in the diagnosis of thyroid nodules

2013 ◽  
Vol 57 (2) ◽  
pp. 89-97 ◽  
Author(s):  
Laura S. Ward ◽  
Richard T. Kloos
Keyword(s):  
Predictive Value ◽  
High Sensitivity ◽  
High Specificity ◽  
Cost Effective ◽  
Needle Aspiration ◽  
Molecular Diagnostic ◽  
Risk Of Malignancy ◽  
Benign Nodules ◽  
Low Sensitivity ◽  
Rule Out

An indeterminate thyroid nodule cytology result occurs about every sixth fine-needle aspiration. These indeterminate nodules harbor a 24% risk of malignancy (ROM); too high to ignore, but driving surgery where most nodules are benign. Molecular diagnostics have emerged to ideally avoid surgery when appropriate, and to trigger the correct therapeutic surgery when indicated, as opposed to an incomplete diagnostic surgery. No current molecular test offers both high sensitivity and high specificity. A molecular diagnostic test with high sensitivity (e.g. Afirma Gene Expression Classifier sensitivity 90%) offers a high Negative Predictive Value when the ROM is relatively low, such as < 30%. Only such tests can "rule-out" cancer. In this setting, a molecularly benign result suggests the same ROM as that of operated cytologically benign nodules (~6%). Thus, clinical observation can replace diagnostic surgery; increasing quality of life and decreasing medical costs. However, its low specificity cannot "rule-in" cancer as a suspicious result has a Positive Predictive Value (PPV) of ~40%, perhaps too low to routinely reflex to definitive cancer surgery. Conversely, high specificity tests (BRAF, RAS, PPAR/PAX-8, RET/PTC, PTEN) offer high PPV results, and only these tests can "rule-in" cancer. Here a positive molecular result warrants definitive therapeutic surgery. However, their low sensitivity cannot "rule-out" cancer and a negative molecular result cannot dissuade diagnostic surgery; limiting their cost-effectiveness. Whether or not there is a useful and cost-effective role to sequentially combine these approaches, or to modify existing approaches, is under investigation.

scholarly journals Reliability of Cobas Amplicor PCR test in detection of Mycobacterium tuberculosis in respiratory and nonorespiratory specimens

2009 ◽  
Vol 66 (12) ◽  
pp. 992-997
Author(s):  
Zorica Lepsanovic ◽  
Dejana Savic ◽  
Branka Tomanovic
Keyword(s):  
Mycobacterium Tuberculosis ◽  
High Sensitivity ◽  
High Specificity ◽  
Diagnostic Methods ◽  
Nucleic Acid Amplification ◽  
Culture Methods ◽  
Predictive Values ◽  
Polymerase Chain ◽  
Low Sensitivity ◽  
Sensitivity Specificity

Background/Aim. Traditional methods for detection of mycobacteria, such as microscopic examination for the presence of acid-fast bacilli and isolation of the organism by culture, have either a low sensitivity and/or specificity, or take weeks before a definite result is available. Molecular methods, especially those based on nucleic acid amplification, are rapid diagnostic methods which combine high sensitivity and high specificity. The aim of this study was to determine the usefulness of the Cobas Amplicor Mycobacterium tuberculosis polymerase chain reaction (CAPCR) assay in detecting the tuberculosis cause in respiratory and nonrespiratory specimens (compared to culture). Methods. Specimens were decontaminated by the N-acetyl-L-cystein- NaOH method. A 500 ?L aliquot of the processed specimen were used for inoculation of L?wenstein-Jensen (L-J) slants, a drop for acid-fast staining, and 100 ?L for PCR. The Cobas Amplicor PCR was performed according to the manufacturer's instructions. Results. A total of 110 respiratory and 355 nonrespiratory specimens were investigated. After resolving discrepancies by reviewing medical history, overall sensitivity, specificity, and positive and negative predictive values for CA-PCR assay compared to culture, were 83%, 100%, 100%, and 96.8%, respectively. In comparison, they were 50%, 99.7%, 87.5%, and 98%, respectively, for the nonrespiratory specimens. The inhibition rate was 2.8% for respiratory, and 7.6% for nonrespiratory specimens. Conclusion. CA-PCR is a reliable assay that enables specialists to start treatment promptly on a positive test result. Lower value for specificity in a group of nonrespiratory specimens is a consequence of an extremely small number of mycobacteria in some of them.

scholarly journals Validation of the French version of the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD)

2020 ◽  
Author(s):  
Alexandra Pham-Scottez ◽  
Bojan Mirkovic ◽  
Lionel Cailhol ◽  
Julien-Daniel Guelfi ◽  
Fernando Perez-Diaz ◽  
...  
Keyword(s):  
Borderline Personality Disorder ◽  
Personality Disorder ◽  
Psychometric Properties ◽  
High Sensitivity ◽  
High Specificity ◽  
Structured Interview ◽  
Screening Instrument ◽  
Borderline Personality ◽  
French Version ◽  
Low Sensitivity

Abstract Background The study examines the psychometric properties of the French version of the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD) created by M. Zanarini to screen borderline personality disorder in clinical and non-clinical populations. Method In this multicentric longitudinal study from the European Network on Borderline Personality Disorder, a sample of 85 adolescent patients from five psychiatric centres and 85 matched controls without psychiatric comorbidity completed the MSI-BPD, French version, and were interviewed with the Structured Interview for DSM-IV Personality (SIDP-IV), in order to assess the presence or absence of borderline personality disorder. Results The MSI-BPD showed excellent internal consistency (α = 0.87 [0.84;0.90]). Compared to the semi-structured reference interview (SIDP-IV), the MSI-BPD showed substantial congruent validity (AUC = 0.93, CI 95%: 0.90 - 0.97). The optimal cut-off point in the present study was 5 or more as it had relatively high sensitivity (0.87) and specificity (0.85). In our sample, the cut-off point (7 or more) proposed by the original developers of the MSI-BPD showed high specificity (0.95) but low sensitivity (0.63). Conclusions The French version of the MSI-BPD is now available, and its psychometric properties are satisfactory. The French version of the MSI-PBD can be used as a screening tool for borderline personality disorder, for clinical purposes or in research studies.

Saturation and Quantization Reduction in Microarray Experiments using Two Scans at Different Sensitivities

2004 ◽  
Vol 3 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Jorge García de la Nava ◽  
Sacha van Hijum ◽  
Oswaldo Trelles
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Dynamic Range ◽  
High Sensitivity ◽  
Data Sets ◽  
Expression Data ◽  
Additional Information ◽  
Sensitivity Measure ◽  
Collateral Effects ◽  
Low Sensitivity

We present a mathematical model to extend the dynamic range of gene expression data measured by laser scanners. The strategy is based on the rather simple but novel idea of producing two images with different scanner sensitivities, obtaining two different sets of expression values: the first is a low-sensitivity measure to obtain high expression values which would be saturated in a high-sensitivity measure; the second, by the converse strategy, obtains additional information about the low-expression levels. Two mathematical models based on linear and gamma curves are presented for relating the two measurements to each other and producing a coherent and extended range of values. The procedure minimizes the quantization relative error and avoids the collateral effects of saturation. Since most of the current scanner devices are able to adjust the saturation level, the strategy can be considered as a universal solution, and not dependent on the image processing software used for reading the DNA chip. Various tests have been performed, on both proprietary and public domain data sets, showing a reduction of the saturation and quantization effects, not achievable by other methods, with a more complete description of gene-expression data and with a reasonable computational complexity.

Study on Diagnostic Values of Astrocyte Elevated Gene 1 (AEG-1) and Glypican 3 (GPC-3) in Hepatocellular Carcinoma

2019 ◽  
Vol 152 (5) ◽  
pp. 647-655 ◽  
Author(s):  
Wenqing Cao ◽  
Meenal Sharma ◽  
Rami Imam ◽  
Jiangzhou Yu
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Sensitivity ◽  
High Specificity ◽  
The Other ◽  
Diagnostic Potential ◽  
Dysplastic Nodules ◽  
Nontumor Tissue ◽  
Diagnostic Values ◽  
Low Sensitivity ◽  
Sensitivity Specificity

Abstract Objectives To investigate the diagnostic potential of AEG-1 and GPC-3 in hepatocellular carcinoma (HCC). Methods AEG-1 and GPC-3 immunohistochemistry were performed on HCC, adjacent nontumor tissue (ANT), and dysplastic nodules (DN). Results H score of AEG-1 or GPC-3 in HCC was significantly higher than in ANT or DN. In HCC, 92% and 54% showed AEG-1 and GPC-3 positivity, respectively. In ANT, 16.2% were AEG-1 and 7.6% GPC-3 positive. AEG-1 staining was mostly diffuse, whereas GPC-3 frequently showed focal staining. AEG-1 alone showed high sensitivity but low specificity and accuracy. GPC-3, on the other hand, showed high specificity but low sensitivity and accuracy. Combination of both stains boosted the sensitivity, specificity, and accuracy to 94.6%, 89.5%, and 90.5%, respectively, when only diffuse staining was considered as positive. Conclusions AEG-1 or GPC-3 alone seemed not an ideal marker for HCC. The combination of AEG-1 and GPC-3 might improve early diagnosis of HCC.

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