Overview of Molecular Testing of Cytology Specimens

2019 ◽  
Vol 64 (1-2) ◽  
pp. 136-146 ◽  
Author(s):  
Min Huang ◽  
Shuanzeng Wei

Objective: Utilizing cytology specimens for molecular testing has attracted increasing attention in the era of personalized medicine. Cytology specimens are clinically easier to access. The samples can be quickly and completely fixed in a very short time of fixation before tissue degradation occurs, compared to hours or days of fixation in surgical pathology specimens. In addition, cytology specimens can be fixed without formalin, which can significantly damage DNA and RNA. All these factors contribute to the superb quality of DNA and RNA in cytology specimens for molecular tests. Study Design: We summarize the most pertinent information in the literature regarding molecular testing in the field of cytopathology. Results: The first part focuses on the types of cytological specimens that can be used for molecular testing, including the advantages and limitations. The second section describes the common molecular tests and their clinical application. Conclusion: Various types of cytology specimens are suitable for many molecular tests, which may require additional clinical laboratory validation.

2018 ◽  
Vol 25 (3) ◽  
pp. R163-R177 ◽  
Author(s):  
Sergio Vargas-Salas ◽  
José R Martínez ◽  
Soledad Urra ◽  
José Miguel Domínguez ◽  
Natalia Mena ◽  
...  

Thyroid cancer is the most frequent endocrine malignancy, and its incidence is increasing. A current limitation of cytological evaluation of thyroid nodules is that 20–25% are reported as indeterminate. Therefore, an important challenge for clinicians is to determine whether an indeterminate nodule is malignant, and should undergo surgery, or benign, and should be recommended to follow-up. The emergence of precision medicine has offered a valuable solution for this problem, with four tests currently available for the molecular diagnosis of indeterminate cytologies. However, efforts to critically analyze the quality of the accumulated evidence are scarce. This systematic review and meta-analysis is aimed to contribute to a better knowledge about the four available molecular tests, their technical characteristics, clinical performance, and ultimately to help clinicians to make better decisions to provide the best care options possible. For this purpose, we address three critical topics: (i) the proper theoretical accuracy, considering the intended clinical use of the test (rule-in vs rule-out) and the impact on clinical decisions; (ii) the quality of the evidence reported for each test (iii) and how accurate and effective have the tests proved to be after their clinical use. Together with the upcoming evidence, this work provides significant and useful information for healthcare system decision-makers to consider the use of molecular testing as a public health need, avoiding unnecessary surgical risks and costs.


2019 ◽  
pp. 41-42
Author(s):  
Ahmadova Esmira Vaqif

Nowadays, assessment of treatments effectiveness carried out by different methods. About 20 years before due to clinical signs we can make a decision about the severity degree of disease, patients health status. However, now it is not enough. The most important lack of this approach is that in this situation patient’s opinion is neglected. Development of medicine, changing of relationship between patients and doctors give birth to a new direction: unilateral approach replaced by mutual cooperation both of sides. Until the last decades of XX century all treatment results, both conservative and surgical, were evaluated due to the clinical, laboratory and instrumental investigations. As officials defined by the World Health Organization, health is a state of complete physical, mental and social wellbeing [6]. So, during the patient’s conditions assessment all these parameters should investigate. Firstly, Errington in 1966 gave an idea about using quality of life for the describing disease effects. Officials this terming in medicine was established in 1977 [3]. Since that time “Quality of life” used widely in the medicine. Today this is one of the common, convenient and informative methods, which allow physicians assess the patient’s status by following the main rule of medicine- to treat the patient, not the disease [2,4,5]. Its advantages are: Comprehensiveness - it covers all aspects of health Dynamism- allow to monitoring patients status Patients participation- this is the main benefit.


Author(s):  
Apostolia M. Tsimberidou ◽  
Ulrik Ringborg ◽  
Richard L. Schilsky

This article highlights major developments over the last decade in personalized medicine in cancer. Emerging data from clinical studies demonstrate that the use of targeted agents in patients with targetable molecular aberrations improves clinical outcomes. Despite a surge of studies, however, significant gaps in knowledge remain, especially in identifying driver molecular aberrations in patients with multiple aberrations, understanding molecular networks that control carcinogenesis and metastasis, and most importantly, discovering effective targeted agents. Implementation of personalized medicine requires continued scientific and technological breakthroughs; standardization of tumor tissue acquisition and molecular testing; changes in oncology practice and regulatory standards for drug and device access and approval; modification of reimbursement policies by health care payers; and innovative ways to collect and analyze electronic patient information that are linked to prospective clinical registries and rapid learning systems. Informatics systems that integrate clinical, laboratory, radiologic, molecular, and economic data will improve clinical care and will provide infrastructure to enable clinical research. The initiative of the EurocanPlatform aims to overcome the challenges of implementing personalized medicine in Europe by sharing patients, biologic materials, and technological resources across borders. The EurocanPlatform establishes a complete translational cancer research program covering the drug development process and strengthening collaborations among academic centers, pharmaceutical companies, regulatory authorities, health technology assessment organizations, and health care systems. The CancerLinQ rapid learning system being developed by ASCO has the potential to revolutionize how all stakeholders in the cancer community assemble and use information obtained from patients treated in real-world settings to guide clinical practice, regulatory decisions, and health care payment policy.


2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Justin L. Kandler ◽  
Alexandra D. Mercante ◽  
Tracy L. Dalton ◽  
Matthew N. Ezewudo ◽  
Lauren S. Cowan ◽  
...  

ABSTRACTResistance to the first-line antituberculosis (TB) drug isoniazid (INH) is widespread, and the mechanism of resistance is unknown in approximately 15% of INH-resistant (INH-R) strains. To improve molecular detection of INH-R TB, we used whole-genome sequencing (WGS) to analyze 52 phenotypically INH-RMycobacterium tuberculosiscomplex (MTBC) clinical isolates that lacked the commonkatGS315T orinhApromoter mutations. Approximately 94% (49/52) of strains had mutations at known INH-associated loci that were likely to confer INH resistance. All such mutations would be detectable by sequencing more DNA adjacent to existing target regions. Use of WGS minimized the chances of missing infrequent INH resistance mutations outside commonly targeted hotspots. We used recombineering to generate 12 observed clinicalkatGmutations in the pansusceptible H37Rv reference strain and determined their impact on INH resistance. Our functional genetic experiments have confirmed the role of seven suspected INH resistance mutations and discovered five novel INH resistance mutations. All recombineeredkatGmutations conferred resistance to INH at a MIC of ≥0.25 μg/ml and should be added to the list of INH resistance determinants targeted by molecular diagnostic assays. We conclude that WGS is a useful tool for detecting uncommon INH resistance mutations that would otherwise be missed by current targeted molecular testing methods and suggest that its use (or use of expanded conventional or next-generation-based targeted sequencing) may provide earlier diagnosis of INH-R TB.


CytoJournal ◽  
2014 ◽  
Vol 11 ◽  
pp. 7 ◽  
Author(s):  
John P. Crapanzano ◽  
Jonas J. Heymann ◽  
Sara Monaco ◽  
Aziza Nassar ◽  
Anjali Saqi

Background: In the recent past, algorithms and recommendations to standardize the morphological, immunohistochemical and molecular classification of lung cancers on cytology specimens have been proposed, and several organizations have recommended cell blocks (CBs) as the preferred modality for molecular testing. Based on the literature, there are several different techniques available for CB preparation-suggesting that there is no standard. The aim of this study was to conduct a survey of CB preparation techniques utilized in various practice settings and analyze current issues, if any. Materials and Methods: A single E-mail with a link to an electronic survey was distributed to members of the American Society of Cytopathology and other pathologists. Questions pertaining to the participants’ practice setting and CBs-volume, method, quality and satisfaction-were included. Results: Of 95 respondents, 90/95 (94%) completed the survey and comprise the study group. Most participants practice in a community hospital/private practice (44%) or academic center (41%). On average, 14 CBs (range 0-50; median 10) are prepared by a laboratory daily. Over 10 methods are utilized: Plasma thrombin (33%), HistoGel (27%), Cellient automated cell block system (8%) and others (31%) respectively. Forty of 90 (44%) respondents are either unsatisfied or sometimes satisfied with their CB quality, with low-cellular yield being the leading cause of dissatisfaction. There was no statistical significance between the three most common CB preparation methods and satisfaction with quality. Discussion: Many are dissatisfied with their current method of CB preparation, and there is no consistent method to prepare CBs. In today's era of personalized medicine with an increasing array of molecular tests being applied to cytological specimens, there is a need for a standardized protocol for CB optimization to enhance cellularity.


2018 ◽  
Author(s):  
Justin L. Kandler ◽  
Alexandra D. Mercante ◽  
Tracy L. Dalton ◽  
Matthew N. Ezewudo ◽  
Lauren S. Cowan ◽  
...  

AbstractResistance to the first-line anti-tuberculosis (TB) drug, isoniazid (INH), is widespread, and the mechanism of resistance is unknown in approximately 15% of INH-resistant (INH-R) strains. To improve molecular detection of INH-R TB, we used whole genome sequencing (WGS) to analyze 52 phenotypically INH-R Mycobacterium tuberculosis complex (MTBC) clinical isolates that lacked the common katG S315T or inhA promoter mutations. Approximately 94% (49/52) of strains had mutations at known INH-associated loci that were likely to confer INH resistance. All such mutations would be detectable by sequencing more DNA adjacent to existing target regions. Use of WGS minimized the chances of missing infrequent INH resistance mutations outside commonly targeted hotspots. We used recombineering to generate 12 observed clinical katG mutations in the pansusceptible H37Rv reference strain and determined their impact on INH resistance. Our functional genetic experiments have confirmed the role of seven suspected INH resistance mutations and discovered five novel INH resistance mutations. All recombineered katG mutations conferred resistance to INH at a minimum inhibitory concentration of ≥0.25 μg/mL and should be added to the list of INH resistance determinants targeted by molecular diagnostic assays. We conclude that WGS is a superior method for detection of INH-R MTBC compared to current targeted molecular testing methods and could provide earlier diagnosis of drug-resistant TB.


DeKaVe ◽  
2013 ◽  
Vol 1 (2) ◽  
Author(s):  
Prayanto WH

Magazine is one of the forms of mass media that has fungsikomunikasi to convey information to mass audiences. The cover is an important element because it is through cover / cover one can guess the contents of the magazine, as well as further interested to know further information contained therein. On a magazine cover consists of drawings and writings are arranged in such a way that looks interesting and has meaning Press publications, especially magazines, today's not enough just to rely on the quality of news or manuscript, although verbal aspect is very important. It must be recognized that the visual aspects (design) as the cover / envelope has crucial role to capture the prospective reader. For the cover of a magazine is a window that shows the content information, can be either a text or photographs, illustrations, and design elements. The function of a magazine cover is to attract, dazzle prospective readers, by way influence the thoughts flow in a short time. So it's no wonder much current the magazine publisher who made the cover of such a way as to attract the attention of prospective readers. Thus the task of designers to magazine cover to create designs that attract the attention of the reader becomes increasingly severe. This study tries to analyze a visual on the front cover Magazine Graphic Design 'Concept' birthday inaugural edition by using the Roland Barthes' semiotic approach. As Roland Barthes (1984), any simple "design work (magazine cover)" continue to play in management of the sign. So that will generate a message (image) specific. Design cover, usually contains the elements of the sign in the form of objects, context of the environment, people or other beings who provide meaning to objects, and text (of writing) that reinforce the meaning.Keyword: cover, magazine Concept, semiotics


2020 ◽  
Vol 26 (11) ◽  
pp. 2567-2593
Author(s):  
M.V. Pomazanov

Subject. The study addresses the improvement of risk management efficiency and the quality of lending decisions made by banks. Objectives. The aim is to present the bank management with a fair algorithm for risk management motivation on the one hand, and the credit management (business) on the other hand. Within the framework of the common goal to maximize risk-adjusted income from loans, this algorithm will provide guidelines for ‘risk management’ and ‘business’ functions on how to improve individual and overall efficiency. Methods. The study employs the discriminant analysis, type I and II errors, Lorentz curve modeling, statistical analysis, economic modeling. Results. The paper offers a mechanism for assessing the quality of risk management decisions as opposed to (or in support of) decisions of the lending business when approving transactions. The mechanism rests on the approach of stating type I and II errors and the corresponding classical metric of the Gini coefficient. On the ‘business’ side, the mechanism monitors the improvement or deterioration of the indicator of changes in losses in comparison with the market average. Conclusions. The study substantiates the stimulating ‘rules of the game’ between the ‘business’ and ‘risk management’ to improve the efficiency of the entire business, to optimize interactions within the framework of internal competition. It presents mathematical tools to calculate corresponding indicators of the efficiency of internally competing entities.


Author(s):  
J Stephen Nix ◽  
Cristiane M Ida

Abstract Molecular testing has become part of the routine diagnostic workup of brain tumors after the implementation of integrated histomolecular diagnoses in the 2016 WHO classification update. It is important for every neuropathologist to be aware of practical preanalytical, analytical, and postanalytical factors that impact the performance and interpretation of molecular tests. Prior to testing, optimizing tumor purity and tumor amount increases the ability of the molecular test to detect the genetic alteration of interest. Recognizing basic molecular testing platform analytical characteristics allows selection of the optimal platform for each clinicopathological scenario. Finally, postanalytical considerations to properly interpret molecular test results include understanding the clinical significance of the detected genetic alteration, recognizing that detected clinically significant genetic alterations are occasionally germline constitutional rather than somatic tumor-specific, and being cognizant that recommended and commonly used genetic nomenclature may differ. Potential pitfalls in brain tumor molecular diagnosis are also discussed.


Sign in / Sign up

Export Citation Format

Share Document