ENDO 2013: The Endocrine Society 95th Annual Meeting & Expo:
Predictive Gene Signature Test for Thyroid Tumors
The American Cancer Society estimates there will be about 60,220 new cases of thyroid cancer in the United States during 2013. Of this number, nearly 45,310 women and 14,910 men may be affected. While "2 out of 3 cases are found in people younger than 55, about 2% of thyroid cancers occur in children and teens."1
Thyroid cancer awareness initiatives and advances in diagnostic practices, such as thyroid ultrasound and fine-needle aspiration (FNA) have increased early detection of thyroid tumors and malignancy. At The Endocrine Society's recent annual meeting (ENDO 2013), Herman Gonzalez, MD, PhD presented the results from his study of a new gene signature that accurately diagnoses benign thyroid growths. Dr. Gonazalez is Associate Professor at Pontifical Catholic University of Chile in Santiago.
While FNA is the diagnostic standard in assessing thyroid nodules, approximately 15% to 20% are indeterminate. In these cases, surgery is often recommended, although only 15% to 25% of thyroid nodules prove to be malignant. The value of the new gene signature is it accurately classifies benign thyroid nodules potentially sparing many patients unnecessary surgeries.
Through an extensive literature search, 18 genes were selected from potential biomarkers related to papillary thyroid cancer (PTC). Samples of PTC and benign thyroid nodules were obtained in the operating room from 215 patients; approximately, 50% were benign and 50% malignant. Gene expression was analyzed using real-time polymerase chain reaction testing. Next, patients were randomly divided into two groups; a training set (68 PTC, 42 benign) and a testing set (38 PTC, 67 benign).
The new gene classifier uses 10 genes. In the training set, sensitivity was 98%, specificity was 93%, positive predictive value (PPV) was 95%, and negative predictive value (NPV) was 96%. The analytical accuracy in the testing set was similar (sensitivity 95%, specificity 90%, PPV 83%, NPV 98%).
In phase two, 65 fresh samples (16 PTC, 49 benign) underwent FNA. The assay correctly identified 62 samples; sensitivity 88%, specificity 96%, PPV 88%, and NPV 96%.
The result from this study is a highly predictive gene signature that identifies patients with benign thyroid nodules that do not require surgical intervention. Furthermore, because the test uses only 10 genes, it could be developed into a kit for point-of-care molecular diagnosis.