scholarly journals Frequency of false-positive FISH 1p/19q codeletion in adult diffuse astrocytic gliomas

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Matthew K Ball ◽  
Thomas M Kollmeyer ◽  
Corinne E Praska ◽  
Michelle L McKenna ◽  
Caterina Giannini ◽  
...  
Keyword(s):  
False Positive ◽  
False Positives ◽  
Chromosomal Microarray ◽  
Who Grade ◽  
Idh1 R132h ◽  
P53 Immunohistochemistry ◽  
Current Classification ◽  
Cautious Interpretation ◽  
Astrocytic Gliomas

Abstract Background Oligodendroglioma is genetically defined by concomitant IDH (IDH1/IDH2) mutation and whole-arm 1p/19q codeletion. Codeletion of 1p/19q traditionally evaluated by fluorescence in situ hybridization (FISH) cannot distinguish partial from whole-arm 1p/19q codeletion. Partial 1p/19q codeletion called positive by FISH is diagnostically a “false-positive” result. Chromosomal microarray (CMA) discriminates partial from whole-arm 1p/19q codeletion. Herein, we aimed to estimate the frequency of partial 1p/19q codeletion that would lead to a false-positive FISH result. Methods FISH 1p/19q codeletion test probe coordinates were mapped onto Oncoscan CMA data to determine the rate of partial 1p/19q codeletion predicted to be positive by FISH. Diffuse astrocytic gliomas with available CMA data (2015–2018) were evaluated and classified based on IDH1-R132H/ATRX/p53 immunohistochemistry, IDH/TERT promoter targeted sequencing, and/or CMA according to classification updates. Predicted false-positive cases were verified by FISH whenever possible. Results The overall estimated false-positive FISH 1p/19q codeletion rate was 3.6% (8/223). Predicted false positives were verified by FISH in 6 (of 8) cases. False-positive rates did not differ significantly (P = .49) between IDH-mutant (4.6%; 4/86) and IDH-wildtype (2.9%; 4/137) tumors. IDH-wildtype false positives were all WHO grade IV, whereas IDH-mutant false positives spanned WHO grades II-IV. Testing for 1p/19q codeletion would not have been indicated for most false positives based on current classification recommendations. Conclusion Selective 1p/19q codeletion testing and cautious interpretation for conflicting FISH and histopathological findings are recommended to avoid potential misdiagnosis.

scholarly journals The Key Reason of False Positive Misclassification for Accurate Large-Area Mangrove Classifications

2021 ◽  
Vol 13 (15) ◽  
pp. 2909
Author(s):  
Chuanpeng Zhao ◽  
Cheng-Zhi Qin
Keyword(s):  
False Positive ◽  
Classification Scheme ◽  
Abundant Species ◽  
Google Earth ◽  
Large Area ◽  
Local Characteristics ◽  
Current Classification ◽  
Standard Classification ◽  
Selected Subset ◽  
Time Series Images

Accurate large-area mangrove classification is a challenging task due to the complexity of mangroves, such as abundant species within the mangrove category, and various appearances resulting from a large latitudinal span and varied habitats. Existing studies have improved mangrove classifications by introducing time series images, constructing new indices sensitive to mangroves, and correcting classifications by empirical constraints and visual inspections. However, false positive misclassifications are still prevalent in current classification results before corrections, and the key reason for false positive misclassification in large-area mangrove classifications is unknown. To address this knowledge gap, a hypothesis that an inadequate classification scheme (i.e., the choice of categories) is the key reason for such false positive misclassification is proposed in this paper. To validate this hypothesis, new categories considering non-mangrove vegetation near water (i.e., within one pixel from water bodies) were introduced, which is inclined to be misclassified as mangroves, into a normally-used standard classification scheme, so as to form a new scheme. In controlled conditions, two experiments were conducted. The first experiment using the same total features to derive direct mangrove classification results in China for the year 2018 on the Google Earth Engine with the standard scheme and the new scheme respectively. The second experiment used the optimal features to balance the probability of a selected feature to be effective for the scheme. A comparison shows that the inclusion of the new categories reduced the false positive pixels with a rate of 71.3% in the first experiment, and a rate of 66.3% in the second experiment. Local characteristics of false positive pixels within 1 × 1 km cells, and direct classification results in two selected subset areas were also analyzed for quantitative and qualitative validation. All the validation results from the two experiments support the finding that the hypothesis is true. The validated hypothesis can be easily applied to other studies to alleviate the prevalence of false positive misclassifications.

scholarly journals IDH1 Non-Canonical Mutations and Survival in Patients with Glioma

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 342 ◽  
Author(s):  
Enrico Franceschi ◽  
Dario De Biase ◽  
Vincenzo Di Nunno ◽  
Annalisa Pession ◽  
Alicia Tosoni ◽  
...  
Keyword(s):  
Idh1 Mutation ◽  
Who Grade ◽  
Tissue Samples ◽  
1P19q Codeletion ◽  
Idh1 R132h ◽  
Rare Mutations ◽  
Grade Ii ◽  
Idh1 Mutations ◽  
R132h Mutation ◽  
Generation Sequencing

Background: Non-canonical mutations of the isocitrate dehydrogenase (IDH) genes have been described in about 20–25% and 5–12% of patients with WHO grade II and III gliomas, respectively. To date, the prognostic value of these rare mutations is still a topic of debate. Methods: We selected patients with WHO grade II and III gliomas and IDH1 mutations with available tissue samples for next-generation sequencing. The clinical outcomes and baseline behaviors of patients with canonical IDH1 R132H and non-canonical IDH1 mutations were compared. Results: We evaluated 433 patients harboring IDH1 mutations. Three hundred and ninety patients (90.1%) had a canonical IDH1 R132H mutation while 43 patients (9.9%) had a non-canonical IDH1 mutation. Compared to those with the IDH1 canonical mutation, patients with non-canonical mutations were younger (p < 0.001) and less frequently presented the 1p19q codeletion (p = 0.017). Multivariate analysis confirmed that the extension of surgery (p = 0.003), the presence of the 1p19q codeletion (p = 0.001), and the presence of a non-canonical mutation (p = 0.041) were variables correlated with improved overall survival. Conclusion: the presence of non-canonical IDH1 mutations could be associated with improved survival among patients with IDH1 mutated grade II–III glioma.

scholarly journals Train Fast While Reducing False Positives: Improving Animal Classification Performance Using Convolutional Neural Networks

Geomatics ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 34-49
Author(s):  
Mael Moreni ◽  
Jerome Theau ◽  
Samuel Foucher
Keyword(s):  
False Positive ◽  
Classification Performance ◽  
Large Datasets ◽  
False Positives ◽  
Fine Tuning ◽  
Training Time ◽  
In The Wild ◽  
Test Sets ◽  
High Level ◽  
Time Decrease

The combination of unmanned aerial vehicles (UAV) with deep learning models has the capacity to replace manned aircrafts for wildlife surveys. However, the scarcity of animals in the wild often leads to highly unbalanced, large datasets for which even a good detection method can return a large amount of false detections. Our objectives in this paper were to design a training method that would reduce training time, decrease the number of false positives and alleviate the fine-tuning effort of an image classifier in a context of animal surveys. We acquired two highly unbalanced datasets of deer images with a UAV and trained a Resnet-18 classifier using hard-negative mining and a series of recent techniques. Our method achieved sub-decimal false positive rates on two test sets (1 false positive per 19,162 and 213,312 negatives respectively), while training on small but relevant fractions of the data. The resulting training times were therefore significantly shorter than they would have been using the whole datasets. This high level of efficiency was achieved with little tuning effort and using simple techniques. We believe this parsimonious approach to dealing with highly unbalanced, large datasets could be particularly useful to projects with either limited resources or extremely large datasets.

scholarly journals A 25-year retrospective, single center analysis of 343 WHO grade II/III glioma patients: implications for grading and temozolomide therapy

2021 ◽  
Author(s):  
Eike Steidl ◽  
Katharina Filipski ◽  
Pia S. Zeiner ◽  
Marlies Wagner ◽  
Emmanouil Fokas ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Molecular Markers ◽  
Treatment Time ◽  
Real Life ◽  
Patient Characteristics ◽  
Low Grade ◽  
Who Grade ◽  
Idh1 R132h ◽  
Treatment Data ◽  
Grade Ii

Abstract Purpose Classification and treatment of WHO grade II/III gliomas have dramatically changed. Implementing molecular markers into the WHO classification raised discussions about the significance of grading and clinical trials showed overall survival (OS) benefits for combined radiochemotherapy. As molecularly stratified treatment data outside clinical trials are scarce, we conducted this retrospective study. Methods We identified 343 patients (1995–2015) with newly diagnosed WHO grade II/III gliomas and analyzed molecular markers, patient characteristics, symptoms, histology, treatment, time to treatment failure (TTF) and OS. Results IDH-status was available for all patients (259 mutant, 84 IDH1-R132H-non-mutant). Molecular subclassification was possible in 173 tumors, resulting in diagnosis of 80 astrocytomas and 93 oligodendrogliomas. WHO grading remained significant for OS in astrocytomas/IDH1-R132H-non-mutant gliomas (p < 0.01) but not for oligodendroglioma (p = 0.27). Chemotherapy (and temozolomide in particular) showed inferior OS compared to radiotherapy in astrocytomas (median 6.1/12.1 years; p = 0.03) and oligodendrogliomas (median 13.2/not reached (n.r.) years; p = 0.03). While radiochemotherapy improved TTF in oligodendroglioma (median radiochemotherapy n.r./chemotherapy 3.8/radiotherapy 7.3 years; p < 0.001/ = 0.06; OS data immature) the effect, mainly in combination with temozolomide, was weaker in astrocytomas (median radiochemotherapy 6.7/chemotherapy 2.3/radiotherapy 2.0 years; p < 0.001/ = 0.11) and did not translate to improved OS (median 8.4 years). Conclusion This is one of the largest retrospective, real-life datasets reporting treatment and outcome in low-grade gliomas incorporating molecular markers. Current histologic grading features remain prognostic in astrocytomas while being insignificant in oligodendroglioma with interfering treatment effects. Chemotherapy (temozolomide) was less effective than radiotherapy in both astrocytomas and oligodendrogliomas while radiochemotherapy showed the highest TTF in oligodendrogliomas.

Laboratory Testing for HER2/neu in Breast Carcinoma: An Evolving Strategy to Predict Response to Targeted Therapy

2001 ◽  
Vol 8 (5) ◽  
pp. 415-418 ◽  
Author(s):  
Nils M. Diaz
Keyword(s):  
Targeted Therapy ◽  
Breast Carcinoma ◽  
Gene Amplification ◽  
Laboratory Testing ◽  
False Positives ◽  
Response To Therapy ◽  
Fish Analysis ◽  
Breast Carcinomas ◽  
Testing Strategies

Background Laboratory testing of HER2/neu in breast carcinoma has become vital to patient care following the approval of trastuzumab as the first therapy to target the HER2/neu oncoprotein. Initial clinical trials used immunohistochemistry (IHC) to test for HER2/neu overexpression in order to select patients for therapy. Fluorescence in situ hybridization (FISH), which tests for gene amplification, is more specific and sensitive than IHC when either assay is compared with HER2/neu overexpression as determined by Northern or Western blot analysis. Many weak overexpressors on IHC testing are not gene amplified on FISH analysis. Such weak overexpressors may be considered false-positives and raise the question of how best to test for HER2/neu. Methods The literature was surveyed regarding testing for HER2/neu overexpression in breast carcinomas and alternative testing strategies. Results False-positive results are a significant problem when IHC is exclusively used to test for HER2/neu overexpression. The false-positives are overwhelmingly confined to the group of 2+ positives and do not respond to targeted therapy. In contrast, concordance between IHC and FISH is high when immunostaining is interpreted as either negative or strongly positive (3+). Whereas some recent studies have suggested that FISH may better predict response to anti-HER2/neu therapy than IHC, others have indicated that IHC is as effective a predictor as FISH. IHC is less technically demanding and costly than FISH. Conclusions IHC analysis of HER2/neu in breast carcinoma is a useful predictor of response to therapy with trastuzumab when strongly positive. Negative immunostaining is highly concordant with a lack of gene amplification by FISH. Most weakly positive overexpressors are false-positives on testing with FISH. Thus, screening of breast carcinomas with IHC and confirmation of weakly positive IHC results by FISH is an effective evolving strategy for testing HER2/neu as a predictor of response to targeted therapy.

Evaluation of Positive T- and B-Cell Gene Rearrangement Studies Among Patients Without a Definitive Diagnosis by Other Assays

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S35-S36
Author(s):  
Hadrian Mendoza ◽  
Christopher Tormey ◽  
Alexa Siddon
Keyword(s):  
T Cell ◽  
False Positive ◽  
Gene Rearrangement ◽  
Hematologic Malignancy ◽  
False Negative ◽  
False Positives ◽  
False Negatives ◽  
True Negative ◽  
Flow Cytometric ◽  
Pathology Reports

Abstract In the evaluation of bone marrow (BM) and peripheral blood (PB) for hematologic malignancy, positive immunoglobulin heavy chain (IG) or T-cell receptor (TCR) gene rearrangement results may be detected despite unrevealing results from morphologic, flow cytometric, immunohistochemical (IHC), and/or cytogenetic studies. The significance of positive rearrangement studies in the context of otherwise normal ancillary findings is unknown, and as such, we hypothesized that gene rearrangement studies may be predictive of an emerging B- or T-cell clone in the absence of other abnormal laboratory tests. Data from all patients who underwent IG or TCR gene rearrangement testing at the authors’ affiliated VA hospital between January 1, 2013, and July 6, 2018, were extracted from the electronic medical record. Date of testing; specimen source; and morphologic, flow cytometric, IHC, and cytogenetic characterization of the tissue source were recorded from pathology reports. Gene rearrangement results were categorized as true positive, false positive, false negative, or true negative. Lastly, patient records were reviewed for subsequent diagnosis of hematologic malignancy in patients with positive gene rearrangement results with negative ancillary testing. A total of 136 patients, who had 203 gene rearrangement studies (50 PB and 153 BM), were analyzed. In TCR studies, there were 2 false positives and 1 false negative in 47 PB assays, as well as 7 false positives and 1 false negative in 54 BM assays. Regarding IG studies, 3 false positives and 12 false negatives in 99 BM studies were identified. Sensitivity and specificity, respectively, were calculated for PB TCR studies (94% and 93%), BM IG studies (71% and 95%), and BM TCR studies (92% and 83%). Analysis of PB IG gene rearrangement studies was not performed due to the small number of tests (3; all true negative). None of the 12 patients with false-positive IG/TCR gene rearrangement studies later developed a lymphoproliferative disorder, although 2 patients were later diagnosed with acute myeloid leukemia. Of the 14 false negatives, 10 (71%) were related to a diagnosis of plasma cell neoplasms. Results from the present study suggest that positive IG/TCR gene rearrangement studies are not predictive of lymphoproliferative disorders in the context of otherwise negative BM or PB findings. As such, when faced with equivocal pathology reports, clinicians can be practically advised that isolated positive IG/TCR gene rearrangement results may not indicate the need for closer surveillance.

scholarly journals The KELT Follow-up Network and Transit False-positive Catalog: Pre-vetted False Positives for TESS

2018 ◽  
Vol 156 (5) ◽  
pp. 234 ◽  
Author(s):  
Karen A. Collins ◽  
Kevin I. Collins ◽  
Joshua Pepper ◽  
Jonathan Labadie-Bartz ◽  
Keivan G. Stassun ◽  
...  
Keyword(s):  
False Positive ◽  
False Positives

Atypical Hepatic Mesenchymal Hamartoma: Histologic Appearance, Immunophenotype, and Molecular Findings

2018 ◽  
Vol 22 (4) ◽  
pp. 365-369 ◽  
Author(s):  
Dina El Demellawy ◽  
James YJ Lee ◽  
Laura McDonell ◽  
David A Dyment ◽  
AS Knisely ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Tandem Duplication ◽  
Benign Neoplasm ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Mesenchymal Hamartoma ◽  
Genetic Abnormality ◽  
Circulating Lymphocytes ◽  
Histopathologic Findings

Hepatic mesenchymal hamartoma is a rare benign neoplasm principally encountered in young children. Its origin is unknown. We report an unusual hepatic mesenchymal hamartoma in a 7-month-old girl, including histopathologic findings, immunophenotype, and karyotype. Chromosomal microarray analysis of tumoral tissue and circulating lymphocytes found 4 copies of a segment at 1q44 and fluorescence in situ hybridization indicated tandem triplication, ascribed to expansion of a paternal tandem duplication. This genetic abnormality may have played a role in pathogenesis.

The Study of the Ontology and Context Verification Based Intrusion Detection Model

2014 ◽  
Vol 644-650 ◽  
pp. 3338-3341 ◽  
Author(s):  
Guang Feng Guo
Keyword(s):  
Intrusion Detection ◽  
Knowledge Base ◽  
False Positive ◽  
Intrusion Detection System ◽  
Detection System ◽  
False Positive Rate ◽  
False Positives ◽  
The Real ◽  
Detection Model ◽  
Positive Rate

During the 30-year development of the Intrusion Detection System, the problems such as the high false-positive rate have always plagued the users. Therefore, the ontology and context verification based intrusion detection model (OCVIDM) was put forward to connect the description of attack’s signatures and context effectively. The OCVIDM established the knowledge base of the intrusion detection ontology that was regarded as the center of efficient filtering platform of the false alerts to realize the automatic validation of the alarm and self-acting judgment of the real attacks, so as to achieve the goal of filtering the non-relevant positives alerts and reduce false positives.

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