Division of Endocrine Surgery, Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
Section of Endocrine Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina3Duke Clinical Research Institute, Durham, North Carolina4Deputy Editor, JAMA Surgery.
JAMA Surg. 2016 Jul 1;151(7):663-70. doi: 10.1001/jamasurg.2016.0825.
Thyroid cancer incidence is increasing, and when fine-needle aspiration biopsy results are cytologically indeterminate, the diagnosis is often still established only after thyroidectomy. Molecular marker testing may be helpful in guiding patient-oriented and tailored management of thyroid nodules and thyroid cancer.
To summarize available data on the use of molecular testing to improve the diagnosis and prognostication of thyroid cancer.
A MEDLINE review was conducted using the primary search terms molecular, thyroid cancer, thyroid nodule, and gene expression classifier in search strings. Articles were restricted to those published between January 1, 2010, and June 1, 2015, inclusive of adult humans, and reported in the English language only.
Of 867 titles screened, 67 articles were further identified for review of the full text. The 2 most studied molecular marker testing techniques for indeterminate thyroid nodules include gene expression classifier analysis and evaluation for somatic mutations or rearrangements that are commonly found in thyroid cancer (7-gene panel). Nodules with benign results on gene expression classifier analysis can be associated with less than a 5% risk of cancer and may be observed, while nodules with positive results on the 7-gene panel may have a higher risk of cancer (80%-100%) and definitive surgery can be recommended. However, cancer prevalence and geographic variations in histologic subtypes may affect accuracy and clinical applicability of both tests. Molecular marker tests such as ThyroSeq version 2.1 are more comprehensive, but they need further validation. Preoperative risk stratification using molecular markers also may be used to better define the optimal extent of thyroidectomy for patients with thyroid cancer.
Molecular markers potentially can augment the diagnostic specificity of fine-needle aspiration biopsy to better differentiate cytologically indeterminate nodules that can be safely observed from cytologically indeterminate nodules that may be associated with differentiated thyroid cancer. Long-term follow-up data are still needed; in the end, patient preference regarding the relative risks and benefits of molecular testing is at the crux of decision making.
甲状腺癌的发病率正在上升，当细针穿刺活检的结果为细胞学不确定时，通常仍需要在甲状腺切除术后才能明确诊断。分子标志物检测可能有助于指导基于患者的个体化和针对性的甲状腺结节和甲状腺癌管理。
总结分子检测在改善甲状腺癌诊断和预后方面的应用数据。
通过使用主要搜索词“分子、甲状腺癌、甲状腺结节和基因表达分类器”进行了 MEDLINE 检索，并在搜索字符串中进行了搜索。文章仅限于 2010 年 1 月 1 日至 2015 年 6 月 1 日之间发表的、包含成年人类的、并仅以英文报告的研究。
在筛选出的 867 个标题中，有 67 篇文章进一步进行了全文审查。用于不确定甲状腺结节的 2 种最有研究价值的分子标志物检测技术包括基因表达分类器分析和体细胞突变或重排的评估，这些突变或重排通常存在于甲状腺癌中（7 基因检测）。基因表达分类器分析结果为良性的结节，癌症风险小于 5%，可以进行观察；而 7 基因检测结果阳性的结节可能具有更高的癌症风险（80%-100%），建议进行明确的手术。然而，癌症的流行情况和组织学亚型的地理差异可能会影响两种检测的准确性和临床适用性。像 ThyroSeq version 2.1 这样的分子标志物检测更为全面，但仍需要进一步验证。使用分子标志物进行术前风险分层，也可以更好地确定甲状腺癌患者甲状腺切除术的最佳范围。
分子标志物可能会提高细针穿刺活检的诊断特异性，以更好地区分细胞学不确定的结节，这些结节可以安全地进行观察，而细胞学不确定的结节可能与分化型甲状腺癌相关。仍需要长期的随访数据；最终，患者对分子检测的相对风险和获益的偏好是决策的关键。
