AFIRMA GEC: MOLECULAR ANALYSIS IN FOLLICULAR THYROID NODULES
Afirma GEC is a gene profiling method able to determine the benign nature of a thyroid nodule and to avoid surgery for the patient with indeterminate thyroid nodule (THY3, Bethesda III or IV).
Thyroid needle aspiration (Fine Needle Aspiration, FNA) allows, in most cases, a definitive diagnosis about thyroid nodule nature. Therefore, a thyroid lesion can be classified as benign or malignant. However, cytology is not able to make this distinction in about 20% of cases. This is the case of nodules with indeterminate cytology (Thy 3a or Thy3f according to British Classification, or Bethesda III (AUS/FLUS) and Bethesda IV (Suspicious for Follicular Neoplasm) accordind to Bethesda Classification. In these cases, the cells present in a benign nodule are substantially indistinguishable from those found in the cancer and only its surgical removal allows a definite definitive diagnosis (with histological examination). Generally, for indeterminate thyroid nodules, surgery is often recommended due to the likelihood that follicular proliferation hides a thyroid tumor. However, it is known that after surgery, as many as 80% of the indeterminate nodules will result to be benign and only 20% malignant. In summary, it is very likely that a patient with an indeterminate nodule will undergo surgery “unnecessarily”.
In order to reduce the number of “unnecessary” surgical interventions, ultrasound methods (elastosonography), immunohistochemistry (galectin-3, HBME-1), genetic mutations (mutations and rearrangements of BRAF, RET/PCT) or molecular genetic tests were evaluated, the last representig the most promising methods.
In this context, the most studied method of gene profiling is Afirma, that is able to determine, with high reliability, the benignity of a cytologically indeterminate thyroid nodule. This method has a negative predictive value of 95%. Basically, if a lesion result to be benign by Afirma, it is very likely that the nodule is really benign (with a > 95% probability, about the same probability that a Thy2 nodule has to be benign).
According to experts, such a high negative predictive value is a sufficient condition for: a) considering a benign nodule with Afirma totally similar to a benign nodule of traditional cytology (Thy2); b) replacing the usual use of surgery with clinical and ultrasonographic follow-up.
To better understand the mechanism on which Afirma is based, it is useful to know some concepts: first of all, what is gene expression. Gene expression is the process by which information encoded in a gene is translated into structures in the cell (proteins, metabolites or ribonucleic acid as RNA). The evaluation of gene expression profiles (GEP) is able to simultaneously study multiple genes and to evaluate how many oth them are activated (or not) based on the production of RNA and proteins present in the tissue. By simultaneously measuring the RNA levels of thousands of genes, GEP is able to provide a snapshot of the gene expression rate in a specific tissue sample. So a gene expression test is not a simple genetic test.
Genetic testing can help evaluate the individual risk of developing a disease in the future. In contrast, gene expression tests measure RNA activity in a body tissue/fluid at a given point in life. Since gene expression (and therefore RNA levels) are dynamic and change as a result of pathological processes or environmental factors, these gene activity patterns can be used to diagnose a disease and to evaluate the effect of therapies in the time.
In the thyroid field, the Afirma Gene Expressione Classifier (Afirma GEC) measures the gene expression of as many as 142 genes and is able to assess any genetic alterations associated with thyroid cancer and thus to distinguish cytologically indeterminate thyroid nodules in two categories: benign and suspicious malignant nodules. Basically it is a gene profiling test able to biologically stratify the risk of cancer in an indeterminate (Thy3a, Thy3f, Bethesda III or Bethesda IV) thyroid nodule and to select patients who are at very low risk of having a tumor (<5%). This is therefore an exclusion test (rule-out). If a nodule is benign to Afirma, malignancy can practically be almost excluded, and therefore the patient can definitely avoid surgery.
The first prospective multicenter study on Afirma was published by Alexander (2012) in a prestigious scientific journal (New England Journal Medicine) and showed that Afirma gene expression classifier (GEC) correctly identifies benign nodules with a very high negative predictive value in thyroid nodules larger than 1 cm. Other studies have confirmed these data, demonstrated its validity and clinical applicability (Walsh 2012) and showed that the use of Afirma had reduced the number of unnecessary surgical interventions (Duik 2012).
Diagnsotic performanece of Afirma has been even increased by its last advanced version (Afirma GSC, Genomic Sequencing Classifier) and Afirma GSC X Atlas (Expression Atlas).
In conclusion, Afirma GSC X Atlas represents the most advanced method currently available worldwide for the genomic analysis of indeterminate thyroid nodules (Thy 3a, Thy3f, Bethesda III (AUS/FLUS), Bethesda IV).
Afirma, provides two possible results on indeterminate thyroid nodules: benign or suspicious for malignant. Afirma GSC, by reclassifying cytologically indeterminate thyroid nodules as benign, avoids unnecessary thyroid surgery and is useful in management of cytologically indeterminate thyroid nodules.
Afirma was developed in the United States and, from the first studies, now it is widespread to other countries.
The EndocrinologiaOggi Center in Rome (Italy), is the first center in Europe where Afirma is clinically and routinately used for stratification of indeterminate thyroid nodules. European patients that prefer a closer place to perform Afirma instead of San Francisco (United States), can do it in Rome (Italy) at a lower price (2400 euros).
For more information about Afirma GSC, click here.
For more information about Afirma GSC X Atlas, click here.
For an appointment for Afirma GSC X Atlas, you can:
– write an email (firstname.lastname@example.org)
– call (0039 0686391386)
– book on line (click here).
Dr. Massimiliano Andrioli
MD, PhD, Endocrinologist
Centro EndocrinologiaOggi, Roma
viale Somalia 33A, Roma
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