RAS 阳性甲状腺结节的可变表型及低风险性质
The variable phenotype and low-risk nature of RAS-positive thyroid nodules.
作者信息
Medici Marco, Kwong Norra, Angell Trevor E, Marqusee Ellen, Kim Matthew I, Frates Mary C, Benson Carol B, Cibas Edmund S, Barletta Justine A, Krane Jeffrey F, Ruan Daniel T, Cho Nancy L, Gawande Atul A, Moore Francis D, Alexander Erik K
机构信息
Thyroid Section, Division of Endocrinology, Hypertension and Diabetes, The Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, PBB-B4 Room 417, Boston, MA, 02115, USA.
Department of Radiology, The Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
出版信息
BMC Med. 2015 Aug 7;13:184. doi: 10.1186/s12916-015-0419-z.
BACKGROUND
Oncogenic mutations are common in thyroid cancers. While the frequently detected RAS-oncogene mutations have been studied for diagnostic use in cytologically indeterminate thyroid nodules, no investigation has studied such mutations in an unselected population of thyroid nodules. No long-term study of RAS-positive thyroid nodules has been performed.
METHODS
We performed a prospective, blinded cohort study in 362 consecutive patients presenting with clinically relevant (>1 cm) thyroid nodules. Fine needle aspiration cytology and mutational testing were obtained for all nodules. Post-operative histopathology was obtained for malignant or indeterminate nodules, and benign nodules were sonographically followed. Histopathological features were compared between RAS- and BRAF-positive malignancies. RAS-positive benign nodules were analyzed for growth or cellular change from prior aspirations.
RESULTS
Overall, 17 of 362 nodules were RAS-positive. Nine separate nodules were BRAF-positive, of which eight underwent surgery and all proved malignant (100%). Out of the 17 RAS-positive nodules, ten underwent surgery, of which eight proved malignant (47%). All RAS-positive malignancies were low risk - all follicular variants of papillary carcinoma, without extrathyroidal extension, metastases, or lymphovascular invasion. RAS-positivity was associated with malignancy in younger patients (P = 0.028). Of the nine RAS-positive benign nodules, five had long-term prospective sonographic follow-up (mean 8.3 years) showing no growth or signs of malignancy. Four of these nodules also had previous aspirations (mean 5.8 years prior), all with similar benign results.
CONCLUSIONS
While RAS-oncogene mutations increase malignancy risk, these data demonstrate a low-risk phenotype for most RAS-positive cancers. Furthermore, cytologically benign, yet RAS-positive nodules behave in an indolent fashion over years. RAS-positivity alone should therefore not dictate clinical decisions.
背景
致癌突变在甲状腺癌中很常见。虽然已对频繁检测到的RAS致癌基因突变进行研究，以用于甲状腺细针穿刺细胞学检查结果不确定的甲状腺结节的诊断，但尚未有研究在未选择的甲状腺结节人群中研究此类突变。尚未对RAS阳性甲状腺结节进行长期研究。
方法
我们对362例连续出现临床相关（>1cm）甲状腺结节的患者进行了一项前瞻性、盲法队列研究。对所有结节进行细针穿刺细胞学检查和突变检测。对恶性或不确定结节进行术后组织病理学检查，对良性结节进行超声随访。比较RAS和BRAF阳性恶性肿瘤的组织病理学特征。分析RAS阳性良性结节与先前穿刺相比的生长或细胞变化。
结果
总体而言，362个结节中有17个为RAS阳性。9个结节为BRAF阳性，其中8个接受了手术，均被证实为恶性（100%）。在17个RAS阳性结节中，10个接受了手术，其中8个被证实为恶性（47%）。所有RAS阳性恶性肿瘤均为低风险——均为乳头状癌的滤泡变体，无甲状腺外侵犯、转移或血管侵犯。RAS阳性与年轻患者的恶性肿瘤相关（P = 0.028）。在9个RAS阳性良性结节中，5个进行了长期前瞻性超声随访（平均8.3年），显示无生长或恶性迹象。其中4个结节之前也进行过穿刺（平均在5.8年前），结果均为良性。
结论
虽然RAS致癌基因突变会增加恶性肿瘤风险，但这些数据表明大多数RAS阳性癌症具有低风险表型。此外，细胞学检查为良性但RAS阳性的结节多年来表现为惰性。因此，仅RAS阳性不应决定临床决策。
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