Taye Aida, Gurciullo Dillon, Miles Brett A, Gupta Ashita, Owen Randall P, Inabnet William B, Beyda Jessica N, Marti Jennifer L
Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY.
Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, NY.
Surgery. 2018 Jan;163(1):97-103. doi: 10.1016/j.surg.2017.07.032. Epub 2017 Nov 16.
Molecular testing with the Thyroseq v2 next generation sequencing panel ("Thyroseq") is used to estimate the risk of cancer in indeterminate thyroid nodules.
We analyzed 156 indeterminate thyroid nodules evaluated with Thyroseq, across 3 institutions. Thyroseq data and surgical pathology were matched via pathologic re-review. A result was considered Thyroseq positive if molecular alterations were annotated on the report with malignancy probability >30%. Performance characteristics were estimated using Bayes theorem.
The Thyroseq-negative call rate was 65% (102/156). On surgical pathology, 16% (10/63) of nodules were malignant. The positive predictive value of a Thyroseq-positive result was 22% (8/37; if 2 noninvasive follicular thyroid neoplasm with papillary-like nuclear features are counted as malignant, 27%, 10/37). There was 1 false-negative result (negative predictive value 96%, 22/23). The most common mutation was NRAS (19/37) with a positive predictive value of 7% (1/15). The positive predictive value of all RAS mutations (HRAS, KRAS, NRAS) was 9% (2/22). The second most common mutation, BRAF V600E, had positive predictive value of 100% (3/3).
We report an external analysis of Thyroseq performance in the evaluation of indeterminate thyroid nodules. These data indicate that Thyroseq is likely to offer high negative predictive value but low positive predictive value. Many genetic alterations appear to be nonspecific for malignancy, and positive results should be interpreted with caution. These findings have implications for the management of indeterminate thyroid nodules profiled with Thyroseq.
使用Thyroseq v2下一代测序面板（“Thyroseq”）进行分子检测，以评估甲状腺结节性质不明时的癌症风险。
我们分析了3家机构中156个经Thyroseq评估的甲状腺结节性质不明的病例。通过病理复查将Thyroseq数据与手术病理进行匹配。如果报告中注释的分子改变的恶性概率>30%，则结果被认为是Thyroseq阳性。使用贝叶斯定理估计性能特征。
Thyroseq阴性检出率为65%（102/156）。手术病理显示，16%（10/63）的结节为恶性。Thyroseq阳性结果的阳性预测值为22%（8/37；如果将2例具有乳头状核特征的非侵袭性滤泡性甲状腺肿瘤计为恶性，则为27%，10/37）。有1例假阴性结果（阴性预测值96%，22/23）。最常见的突变是NRAS（19/37），阳性预测值为7%（1/15）。所有RAS突变（HRAS、KRAS、NRAS）的阳性预测值为9%（2/22）。第二常见的突变是BRAF V600E，阳性预测值为100%（3/3）。
我们报告了Thyroseq在评估甲状腺结节性质不明时的性能的外部分析。这些数据表明，Thyroseq可能具有较高的阴性预测值，但阳性预测值较低。许多基因改变似乎对恶性肿瘤不具有特异性，阳性结果应谨慎解释。这些发现对使用Thyroseq分析的甲状腺结节性质不明的管理具有重要意义。
