Kwon Hyemi, Kim Won Gu, Eszlinger Markus, Paschke Ralf, Song Dong Eun, Kim Mijin, Park Suyeon, Jeon Min Ji, Kim Tae Yong, Shong Young Kee, Kim Won Bae
Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Division of Endocrinology and Metabolism, Department of Oncology and Arnie Charbonneau Cancer Institute, Cummings School of Medicine, University of Calgary, Calgary, AB, Canada.
Endocrinol Metab (Seoul). 2016 Dec;31(4):586-591. doi: 10.3803/EnM.2016.31.4.586. Epub 2016 Nov 4.
Molecular analysis for common somatic mutations in thyroid cancer can improve diagnostic accuracy of fine-needle aspiration cytology (FNAC) in the nondiagnostic or indeterminate category of thyroid nodules. In this study, we evaluated the feasibility of molecular diagnosis from residual liquid-based cytology (LBC) material after cytological diagnosis.
This prospective study enrolled 53 patients with thyroid nodules diagnosed as nondiagnostic, atypia of undetermined significance (AUS), or follicular lesion of undetermined significance (FLUS) after FNAC. DNAs and RNAs were isolated from residual LBC materials. BRAF(V600E) and RAS point mutations, PAX8/peroxisome proliferator-activated receptor γ (PPARγ), RET/PTC1, and RET/PTC3 rearrangements were evaluated by real-time polymerase chain reaction and pyrosequencing.
All DNAs from 53 residual LBC samples could be analysed and point mutations were detected in 10 samples (19%). In 17 AUS nodules, seven samples (41%) had point mutations including BRAF (n=4), NRAS (n=2), and KRAS (n=1). In 20 FLUS nodules, three samples (15%) had NRAS point mutations. RNA from only one FLUS nodule could be analysed for rearrangements and there was no abnormality.
Molecular analysis for BRAF and RAS mutations was feasible in residual LBC materials and might be useful for diagnosis of indeterminate thyroid nodules.
甲状腺癌常见体细胞突变的分子分析可提高甲状腺结节非诊断性或意义不明确类别细针穿刺活检（FNAC）的诊断准确性。在本研究中，我们评估了在细胞学诊断后从残留的液基细胞学（LBC）材料进行分子诊断的可行性。
这项前瞻性研究纳入了53例经FNAC诊断为非诊断性、意义不明确的非典型性（AUS）或意义不明确的滤泡性病变（FLUS）的甲状腺结节患者。从残留的LBC材料中分离DNA和RNA。通过实时聚合酶链反应和焦磷酸测序评估BRAF（V600E）和RAS点突变、PAX8/过氧化物酶体增殖物激活受体γ（PPARγ）、RET/PTC1和RET/PTC3重排。
53份残留LBC样本的所有DNA均可进行分析，10份样本（19%）检测到点突变。在17个AUS结节中，7份样本（41%）存在点突变，包括BRAF（n = 4）、NRAS（n = 2）和KRAS（n = 1）。在20个FLUS结节中，3份样本（15%）存在NRAS点突变。仅对1个FLUS结节的RNA进行了重排分析，未发现异常。
对残留LBC材料进行BRAF和RAS突变的分子分析是可行的，可能有助于诊断意义不明确的甲状腺结节。
