scholarly journals Short report: Performance evaluation of the Idylla™ KRAS and EGFR mutation tests on paraffin-embedded cytological NSCLC samples

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Saskia Offerman ◽  
Clemens F. Prinsen ◽  
Ageeth Knol ◽  
Natalie Methorst ◽  
Jeanette Kamphorst ◽  
...  

Abstract Background Quick and reliable testing of EGFR and KRAS is needed in non-small cell lung cancer (NSCLC) to ensure optimal decision-making for targeted therapy. The Idylla™ platform was designed for Formalin-Fixed Paraffin-Embedded (FFPE) tissue sections but recently several studies were published that evaluated its potential for cytological specimens. This study aimed to validate the Idylla™ platform for the detection of EGFR/KRAS mutations in cytological NSCLC samples prepared as cytoblocks using AGAR and paraffin embedding. Material and methods The KRAS Idylla™ test were performed on 11 specimens with a known KRAS mutation. The EGFR Idylla™ test was performed on 18 specimens with a known primary EGFR mutation and 7 specimens with a primary EGFR-EGFR T790M resistance mutation combination. Results Concordant KRAS and primary EGFR mutations were detected for both KRAS and primary EGFR mutations. Samples with a total CQ value of < 26 could be considered negative. Samples with a total CQ value of > 26 could not be assessed (probability of false-negative). In specimens with a primary EGFR-EGFR T790M resistance mutation combination, 5/7 cases were not concordant. Conclusion Our results confirm the conclusion of recent reports that the Idylla™EGFR assay is not suitable in a resistance to EGFR TKI setting, also not in our cytological NSCLC samples prepared as cytoblocks using AGAR and paraffin embedding. KRAS and primary EGFR mutations were detected using the Idylla™ assays in virtually all cytological NSCLC samples. This analysis was rapid and time-saving compared to other mutation detection assays and may be useful if the amount of material is insufficient to perform a full set of molecular tests.

Stat ◽  
2021 ◽  
Author(s):  
Hengrui Cai ◽  
Rui Song ◽  
Wenbin Lu

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Kyoko Yoshizaki ◽  
Akihiro Hirata ◽  
Hiroyuki Matsushita ◽  
Naohito Nishii ◽  
Mifumi Kawabe ◽  
...  

Abstract Background The prevalence of gastrointestinal (GI) neoplastic polyps in Jack Russell terriers (JRTs) has increased in Japan since the late 2000s. Recently, we demonstrated that JRTs with GI polyps harbor identical germline variant in the APC gene (c.[462_463delinsTT]) in the heterozygous state. Thus, this disease is an autosomal dominant hereditary disorder. Although the affected JRTs have distinct features, such as the development of multiple GI polyps and an early age of disease onset, genetic testing is indispensable for a definitive diagnosis. Here, polymerase chain reaction (PCR)-based assays capable of detecting germline APC variant were designed and validated using synthetic wild-type and mutant DNAs and genomic DNAs from carrier and non-carrier dogs. Result First, the PCR-restriction fragment length polymorphism (PCR-RFLP) assay was developed by taking advantage of the germline APC variant creating a new restriction site for MseI. In the PCR-RFLP assay, the 156-bp region containing the variant site was amplified by PCR and subsequently digested with MseI, yielding diagnostic 51 and 58 bp fragments from the mutant allele and allowing determination of the APC genotypes. It was possible to determine the genotypes using genomic DNA extracted from the peripheral blood, buccal swab, or formalin-fixed paraffin-embedded tissue. Next, a TaqMan duplex real-time PCR assay was developed, where a 78-bp region flanking the variant was amplified in the presence of wild-type allele- and mutant allele-specific fluorescent probes. Using blood-derived DNA, altogether 40 cycles of PCR amplification determined the APC genotypes of all examined samples by measuring the fluorescence intensities. Importantly, false-positive and false-negative errors were never detected in both assays. Conclusion In this study, we developed highly reliable genetic tests for hereditary GI polyposis in JRTs, providing accurate assessment of the presence of the causative germline APC variant. The genotyping assays could contribute to the diagnosis and prevention of hereditary GI polyposis in dogs.


Kybernetes ◽  
2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Guangsheng Zhang ◽  
Xiao Wang ◽  
Zhiqing Meng ◽  
Qirui Zhang ◽  
Kexin Wu

PurposeTo remedy the inherent defect in current research that focuses only on a single type of participants, this paper endeavors to look into the situation as an evolutionary game between a representative Logistics Service Integrator (LSI) and a representative Functional Logistics Service Provider (FLSP) in an environment with sudden crisis and tries to analyze how LSI supervises FLSP's operations and how FLSP responds in a recurrent pattern with different interruption probabilities.Design/methodology/approachRegarding the risks of supply chain interruption in emergencies, this paper develops a two-level model of single LSI and single FLSP, using Evolutionary Game theory to analyze their optimal decision-making, as well as their strategic behaviors on different risk levels regarding the interruption probability to achieve the optimal return with bounded rationality.FindingsThe results show that on a low-risk level, if LSI increases the degree of punishment, it will fail to enhance FLSP's operational activeness in the long term; when the risk rises to an intermediate level, a circular game occurs between LSI and FLSP; and on a high level of risk, FLSP will actively take actions, and its functional probability further impacts LSI's strategic choices. Finally, this paper analyzes the moderating impact of punishment intensity and social reputation loss on the evolutionary model in emergencies and provides relevant managerial implications.Originality/valueFirst, by taking both interruption probability and emergencies into consideration, this paper explores the interactions among the factors relevant to LSI's and FLSP's optimal decision-making. Second, this paper analyzes the optimal evolutionary game strategies of LSI and FLSP with different interruption probability and the range of their optimal strategies. Third, the findings of this paper provide valuable implications for relevant practices, such that the punishment intensity and social reputation loss determine the optimal strategies of LSI and FLSP, and thus it is an effective vehicle for LSSC system administrator to achieve the maximum efficiency of the system.


2021 ◽  
pp. 103418
Author(s):  
Xiangqian Zhu ◽  
Wenfeng Wang ◽  
Suhong Pang ◽  
Chaoyin An ◽  
Xiaoliang Yang ◽  
...  

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