A retrospective analysis of the performance of the RosettaGX^® Reveal™ thyroid miRNA and the Afirma Gene Expression Classifiers in a cohort of cytologically indeterminate thyroid nodules

Abstract

Background Molecular tests are increasingly used to triage cytologically indeterminate thyroid nodules for surgery and/or follow‐up. We retrospectively compared the performance of the Afirma Gene Expression Classifier (AGEC) with that of the more recently developed RosettaGX® Reveal™ miRNA Classifier (Reveal) in a cohort of Bethesda III–V thyroid FNAs with surgical follow‐up. Design Eighty‐one samples (54 Bethesda III, 26 Bethesda IV, 1 Bethesda V) with available AGEC (74 AGEC‐SUSP and 7 AGEC‐BENIGN) and surgical pathology results were studied from three academic centers. Reveal was performed in a blinded fashion. Results The final diagnoses were benign/NIFTP (n = 63) and malignant (n = 18). The overall “correct” rate was 64.2% for Reveal and 28.4% for AGEC (P = 1.4e‐6). The specificity of Reveal was 60.3%, compared with 9.5% for AGEC (P = 2.1e‐9). Among the 18 malignant cases, 77.8% and 94.4% were correctly classified as suspicious by Reveal and AGEC, respectively (P = 0.2). In the FLUS and the FN group, the specificity of AGEC was lower than the specificity of Reveal. Whether the 7 NIFTP in our study were considered benign or malignant, specificity and PPV of Reveal were higher than those of AGEC. Reveal also outperformed AGEC in correctly classifying the 26 benign Hürthle lesions studied (P = 7.6e‐5). Conclusion Reveal outperformed AGEC in this cohort, whether NIFTP is considered benign or malignant, and in Hürthle lesions. Reveal has the potential to reduce the number of unnecessary resections in patients with indeterminate thyroid cytology. Based on our findings and the practical advantages offered by Reveal methodology, large prospective studies are warranted. Diagn. Cytopathol.

Risk of malignancy and neoplasia predicted by three molecular testing platforms in indeterminate thyroid nodules on fine‐needle aspiration

“…Our institutional benign rate for Afirma was 31% (21/68). This is comparable to several studies reporting benign call rates ranging from 27% to 54% in their patient populations . However, most cases were followed with observation and excluded from the final data set (Figure and Table ).…”

“…All were benign on resection (one nodular hyperplasia and two follicular adenomas) (Table ). Even though the overall number is small, it is within the range of published excision rates of Afirma‐benign cases (7‐17%) …”

“…In contrast, there is little data published regarding the use of RosettaGX Reveal in clinical practice . The initial validation studies and our personal experience support its utility as a rule‐out test based on the miRNA expression profile in thyroid aspirates .…”

“…Its high NPV and low PPV were promoted to foster its use as a rule‐out test . Since its release as a novel testing platform, several authors have investigated the utility of Afirma GEC and its performance in clinical practice . Single institutional studies and large meta‐analyses of data demonstrated a compelling reduction in the number of unnecessary surgical operations .…”

“…The local prevalence of malignancy has a direct impact on a test's performance. The growing literature unveils several studies that call into question the wholehearted trust in Afirma results . Many authors promote a careful approach to using the data gleaned from molecular tests.…”