Division of Diabetes, Endocrinology, and Metabolism, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska.
Division of Endocrinology, Diabetes and Metabolism, Keck School of Medicine, University of Southern California, Los Angles, California.
Thyroid. 2019 Nov;29(11):1594-1605. doi: 10.1089/thy.2019.0278. Epub 2019 Sep 27.
Gene panels are routinely used to assess predisposition to hereditary cancers by simultaneously testing multiple susceptibility genes and/or variants. More recently, genetic panels have been implemented as part of solid tumor malignancy testing assessing somatic alterations. One example is targeted variant panels for thyroid nodules that are not conclusively malignant or benign upon fine-needle aspiration (FNA). We systematically reviewed published studies from 2009 to 2018 that contained genetic data from preoperative FNA specimens on cytologically indeterminate thyroid nodules (ITNs) that subsequently underwent surgical resection. Pooled prevalence estimates per gene and variant, along with their respective positive predictive values (PPVs) for malignancy, were calculated. Our systematic search identified 540 studies that were supplemented by 18 studies from bibliographies or personal files. Sixty-one studies met all inclusion criteria and included >4600 ITNs. Overall, 26% of nodules contained at least 1 variant or fusion. However, half of them did not include details on the specific gene, variant, and/or complete fusion pair reported for inclusion toward PPV calculations. The PPVs of genomic alterations reported at least 10 times were limited to (98%, 95% confidence interval [CI 96-99%]), (55% [CI 34-78%]), (45% [CI 22-72%]), (42% [CI 19-68%]), and (38% [CI 23-55%]). Excluding , the pooled PPV for all other specified variants and fusions was 47%. Multiple variants within the same nodule were identified in ∼1% of ITN and carried a cumulative PPV of 77%. The chance that a genomic alteration predicts malignancy depends on the individual variant or fusion detected. Only five alterations were reported at least 10 times; had a PPV of 98%, while the remaining four had individual PPVs ranging from 38% to 55%. The small sample size of most variants and fusion pairs found among ITNs, however, limits confidence in their individual PPV point estimates. Better specific reporting of genomic alterations with cytological category, histological subtype, and cancer staging would facilitate better understanding of cancer prediction, and the independent contribution of the genomic profile to prognosis.
基因面板通常用于通过同时测试多个易感性基因和/或变体来评估遗传性癌症的易感性。最近，遗传面板已作为评估体细胞改变的实体瘤恶性肿瘤检测的一部分实施。一个例子是甲状腺结节的靶向变异面板，这些结节在细针抽吸 (FNA) 后不能明确为恶性或良性。我们系统地回顾了 2009 年至 2018 年发表的研究，这些研究包含了术前 FNA 标本中细胞学不确定的甲状腺结节 (ITN) 的遗传数据，随后这些结节接受了手术切除。计算了每个基因和变体的汇总患病率估计值及其恶性的相应阳性预测值 (PPV)。我们的系统搜索确定了 540 项研究，并通过参考文献或个人档案中的 18 项研究进行了补充。61 项研究符合所有纳入标准，包括>4600 个 ITN。总体而言，26%的结节至少包含 1 个变体或融合。然而，其中一半没有包含报告的特定基因、变体和/或完整融合对的详细信息，以便纳入 PPV 计算。至少报告了 10 次的基因组改变的 PPV仅限于 (98%，置信区间 [CI 96-99%])、 (55%[CI 34-78%])、 (45%[CI 22-72%])、 (42%[CI 19-68%])和 (38%[CI 23-55%])。不包括 ，所有其他指定变体和融合的汇总 PPV 为 47%。在约 1%的 ITN 中发现了同一结节内的多个变体，累积 PPV 为 77%。基因组改变预测恶性的可能性取决于检测到的单个变体或融合。只有五种改变至少报告了 10 次； 有 98%的 PPV，而其余四个有 38%至 55%的个体 PPV。然而，大多数 ITN 中的变体和融合对的样本量很小，限制了对其个体 PPV 点估计的置信度。更好地报告具有细胞学分类、组织学亚型和癌症分期的基因组改变将有助于更好地理解癌症预测，以及基因组谱对预后的独立贡献。
