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高侵袭性端粒酶逆转录酶(TERT)启动子突变型甲状腺乳头状癌的超声预测

Ultrasonographic prediction of highly aggressive telomerase reverse transcriptase (TERT) promoter-mutated papillary thyroid cancer.

作者信息

Kim Tae Hyuk, Ki Chang-Seok, Hahn Soo Yeon, Oh Young Lyun, Jang Hye Won, Kim Sun Wook, Chung Jae Hoon, Shin Jung Hee

机构信息

Division of Endocrinology & Metabolism, Department of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

出版信息

Endocrine. 2017 Aug;57(2):234-240. doi: 10.1007/s12020-017-1340-3. Epub 2017 Jun 14.

Abstract

PURPOSE

Telomerase reverse transcriptase promoter mutations are found in highly aggressive thyroid malignancies. Our aim was to define the ultrasonographic features of telomerase reverse transcriptase promoter-mutated papillary thyroid cancer and to evaluate their predictive performances.

METHODS

Ultrasonographic findings were reviewed for 185 patients with surgically confirmed papillary thyroid cancer between 1994 and 2004. Genomic DNA to identify telomerase reverse transcriptase promoter mutations was extracted from archived surgical specimens. Logistic regression analysis was performed to compare clinical factors and ultrasonographic findings between telomerase reverse transcriptase promoter-mutated and wild-type papillary thyroid cancers.

RESULTS

A telomerase reverse transcriptase promoter mutation was detected in 8.1% (15 of 185) of specimens from papillary thyroid cancer patients with a strong trend toward increasing age. Nonparallel orientation and microlobulated margin were independent ultrasonographic findings for predicting telomerase reverse transcriptase promoter-mutated papillary thyroid cancer in patients over 50 years (odds ratio 5.898, 95% confidence interval 1.092-31.851, P = 0.039 for orientation; odds ratio 5.813, 95% confidence interval 1.320-25.602, P = 0.020 for margin). Prevalence of telomerase reverse transcriptase promoter mutations increased to 50.0% in papillary thyroid cancer patients older than 50 years with both ultrasonographic findings and was 0% in patients without either finding. For identifying telomerase reverse transcriptase promoter-mutated papillary thyroid cancer, ultrasonographic had 64.3% sensitivity, 80.8% specificity, 50.0% positive predictive value and 88.4% negative predictive value.

CONCLUSIONS

Telomerase reverse transcriptase promoter-mutated papillary thyroid cancer could be suggested by the ultrasonographic features of nonparallel orientation and microlobulated margin in patients older than 50 years. Prebiopsy recognition of this unique ultrasonographic pattern would mandate the nodule fall into a "biopsy suggested" category.

摘要

目的

端粒酶逆转录酶启动子突变见于侵袭性很强的甲状腺恶性肿瘤中。我们的目的是明确端粒酶逆转录酶启动子突变的甲状腺乳头状癌的超声特征,并评估其预测效能。

方法

回顾性分析1994年至2004年间185例经手术确诊的甲状腺乳头状癌患者的超声检查结果。从存档的手术标本中提取用于鉴定端粒酶逆转录酶启动子突变的基因组DNA。进行逻辑回归分析,比较端粒酶逆转录酶启动子突变型和野生型甲状腺乳头状癌之间的临床因素和超声检查结果。

结果

在甲状腺乳头状癌患者的标本中,8.1%(185例中的15例)检测到端粒酶逆转录酶启动子突变,且有随年龄增长而增加的强烈趋势。非平行方向和微叶状边缘是预测50岁以上患者端粒酶逆转录酶启动子突变型甲状腺乳头状癌的独立超声表现(方向的比值比为5.898,95%置信区间为1.092 - 31.851,P = 0.039;边缘的比值比为5.813,95%置信区间为1.320 - 25.602,P = 0.020)。在50岁以上同时具有这两种超声表现的甲状腺乳头状癌患者中,端粒酶逆转录酶启动子突变的患病率增至50.0%,而在无任何一种表现的患者中为0%。对于识别端粒酶逆转录酶启动子突变型甲状腺乳头状癌,超声检查的敏感性为64.3%,特异性为80.8%,阳性预测值为50.0%,阴性预测值为88.4%。

结论

50岁以上患者端粒酶逆转录酶启动子突变型甲状腺乳头状癌可通过非平行方向和微叶状边缘的超声特征提示。活检前识别这种独特的超声模式将使该结节归入“建议活检”类别。

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