Validation and Multicenter Clinical Experience of the Afirma® Gene Expression Classifier

2014 ◽  
Vol 10 (02) ◽  
pp. 117 ◽  
Author(s):  
Trevor E Angell ◽  
Erik K Alexander ◽  
◽  

The current assessment of clinically relevant thyroid nodules is imprecise and nonspecific, primarily due to the presence of indeterminate cytology. This cytologic category implies a low but clinically important risk for thyroid cancer, historically prompting consideration for diagnostic thyroidectomy in most patients. Over the last 5 years, novel molecular testing options have become available and appear able to modify preoperative thyroid cancer risk and better inform clinical decisions. The Afirma® gene expression classifier (GEC) measures messenger RNA (mRNA) expression patterns in fine-needle aspiration (FNA) tissue and seeks to identify a benign signature despite indeterminate cytology. When detected, the cancer risk is low and allows for prevention of unnecessary surgeries. The results of a large, multicenter, blinded validation trial of the Afirma GEC demonstrated the test’s high negative predictive value. Subsequent independent studies of the Afirma GEC in clinical use have documented the influence these results have on preoperative management recommendations. This review summarizes the current data regarding the Afirma GEC, including the original validation trial and recent multicenter clinical experience.

2015 ◽  
Vol 11 (1) ◽  
pp. 117
Author(s):  
Trevor E Angell ◽  
Erik K Alexander ◽  
◽  

The current assessment of clinically relevant thyroid nodules is imprecise and nonspecific, primarily due to the presence of indeterminate cytology. This cytologic category implies a low but clinically important risk for thyroid cancer, historically prompting consideration for diagnostic thyroidectomy in most patients. Over the last 5 years, novel molecular testing options have become available and appear able to modify preoperative thyroid cancer risk and better inform clinical decisions. The Afirma® gene expression classifier (GEC) measures messenger RNA (mRNA) expression patterns in fine-needle aspiration (FNA) tissue and seeks to identify a benign signature despite indeterminate cytology. When detected, the cancer risk is low and allows for prevention of unnecessary surgeries. The results of a large, multicenter, blinded validation trial of the Afirma GEC demonstrated the test’s high negative predictive value. Subsequent independent studies of the Afirma GEC in clinical use have documented the influence these results have on preoperative management recommendations. This review summarizes the current data regarding the Afirma GEC, including the original validation trial and recent multicenter clinical experience.


Endocrine ◽  
2018 ◽  
Vol 59 (3) ◽  
pp. 573-584 ◽  
Author(s):  
Ghobad Azizi ◽  
James M. Keller ◽  
Michelle L. Mayo ◽  
Kelé Piper ◽  
David Puett ◽  
...  

Oncogene ◽  
2004 ◽  
Vol 23 (44) ◽  
pp. 7436-7440 ◽  
Author(s):  
Milo Frattini ◽  
Cristina Ferrario ◽  
Paola Bressan ◽  
Debora Balestra ◽  
Loris De Cecco ◽  
...  

2014 ◽  
Vol 99 (1) ◽  
pp. 119-125 ◽  
Author(s):  
Erik K. Alexander ◽  
Melanie Schorr ◽  
Joshua Klopper ◽  
Caroline Kim ◽  
Jennifer Sipos ◽  
...  

2021 ◽  
Author(s):  
Rodrigo Giglioti ◽  
Bianca Tainá Azevedo ◽  
Henrique Nunes de Oliveira ◽  
Luciana Morita Katiki ◽  
Anibal Eugênio Vercesi Filho ◽  
...  

Abstract Background: High quality and quantity of messenger RNA (mRNA) are required for accuracy of gene expression studies and other RNA-based downstream applications. Since RNA is considered a labile macromolecular prone to degradation, which may result in falsely altered gene expression patterns, several commercial stabilizing reagents have been developed aiming to keep RNA stable for long period. However, for studies involving large number of experimental samples, the high costs related to these specific reagents may constitute a barrier. Methods and Results: In this context the present study was designed aiming to evaluate the stability of mRNA in whole bovine blood collected in EDTA tubes during storage at common fridge (4°C). Whole blood samples were collected from six Holstein calves and submitted to RNA extraction in each different interval: immediately after blood sampling (< 2 h), at 1-day post-sampling (dps), 2 dps, 3 dps, 7 dps and 14dps intervals. RNA integrity and purity were evaluated, and RT-qPCR assays were run using seven different genes (B2M, ACTB, PPIA, GAPDH, YWHAZ, CD4 and IFN-γ) aiming to evaluate the presence of altered gene transcription during storage. All extracted RNA samples presented high purity, while optimal integrity and unaltered gene expression were observed in whole experimental group up to 3 days of storage.Conclusion: Bovine blood RNA remained stable in K3EDTA tubes for 3 days stored at common fridge and can be successfully and accurately used for gene expression studies.


Cartilage ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 459-466
Author(s):  
Carolin Melcher ◽  
Birte Sievers ◽  
Nadine Höchsmann ◽  
Frank Düren ◽  
Volkmar Jansson ◽  
...  

PurposeThe present study investigated the effects of hyperbaric oxygen (HBO) on human chondrocyte proliferation and gene expression patterns.MethodsChondrocyte cultures were transferred to a HBO chamber and exposed to 100% oxygen for 7 consecutive days. Within groups, pressure was varied between 1 and 2 atm and duration of HBO administration was varied among 60, 90, and 120 minutes. Cell counts were performed using the WST-1 assay at 1, 3, 5, and 7 days after initiation of HBO treatment to obtain data to plot a growth curve. Gene expression of apoptosis markers PARP and caspase 3, as well as cartilage specific proteins collagen II and COMP, were detected by reverse transcription polymerase chain reaction.ResultsThe experiments showed that in vitro administration of HBO inhibit chondrocyte growth. When applied compression was increased up to 2 atm, chondrocyte cell count was reduced by half at days 3 and 7 in association with an upregulation of the apoptosis markers PARP and caspase 3 as well as the cartilage specific proteins collagen II and COMP. No significant differences were monitored from varied duration of daily treatment.ConclusionChondrocyte growth was inhibited in vitro by treatment of HBO. This inhibitory effect was even increased by elevating the applied pressure, while molecular testing showed reduced chondrocyte growth. Higher levels of HBO inhibited cell growth even more, but up-regulation of apoptosis specific markers and cartilage specific proteins were seen during administration of high oxygen levels. Thus, it has to be evaluated that there is a critical level of hypo-/hyperoxia required to stimulate or at least maintain chondrocyte cell proliferation.


2020 ◽  
Vol 148 (4) ◽  
pp. 884-894
Author(s):  
Emilio Ugalde‐Morales ◽  
Felix Grassmann ◽  
Keith Humphreys ◽  
Jingmei Li ◽  
Mikael Eriksson ◽  
...  

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