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摘要: 目的 分析甲状腺乳头状癌(papillary thyroid carcinoma，PTC)多基因检测结果与临床特征的关系。方法 纳入2021年8月-2022年5月在上海交通大学医学院附属仁济医院接受甲状腺切除手术的患者，使用8基因试剂盒检测肿瘤组织，分析基因突变与病例特征的相关性。结果 161例患者中BRAF V600E、RET/PTC1和TERT启动子突变比例分别为82.0%、6.8%和4.3%，BRAF V600E突变常见于男性患者(P=0.023)，TERT启动子突变肿瘤直径大(P=0.019)、多灶性比例高(P=0.050)、淋巴结转移多(P=0.031)。在89例完成术前穿刺BRAF V600E检测的患者中，术前穿刺检测与术后试剂盒检测结果具有较强一致性(Cohen κ=0.694，95%CI：0.482~0.906，P < 0.01)。观察获得苏木精-伊红染色切片的80例患者，基因突变类型以BRAF V600E为主，经典或滤泡型分布较多，TERT启动子突变和RET/PTC1融合则分别以高细胞/柱状/靴钉型和弥漫硬化型为主要病理亚型。单因素方差分析显示不同病理亚型间的患病年龄(P=0.029)和肿瘤直径(P < 0.01)存在差异。结论 多基因试剂盒作为一种简便易行的PTC临床检测手段，能够补充识别BRAF V600E点突变以外的重要基因事件，为术后患者提供更多预后信息及随访提示。Abstract: Objective To analyze the clinical significance of multigene assay in papillary thyroid carcinoma(PTC).Methods Patients who underwent thyroidectomy in a tertiary hospital from August 2021 to May 2022 were enrolled. The eight-gene panel was used to detect the tumor tissue of patients, and the correlation between gene mutations and clinical features was analyzed.Results Among 161 patients, mutation rate of BRAF V600E, RET/PTC1 and TERT promotor were 82.0%, 6.8% and 4.3%, respectively. BRAF V600E mutation was more common in male patients(P=0.023). TERT promotor-mutated tumors had a large diameter(P=0.019), a high proportion of multifocal lesions(P=0.050), and a large number of lymph node metastases(P=0.031). Among 89 patients who completed preoperative BRAF detection, there was a strong consistency between the preoperative aspiration test and postoperative panel(Cohen κ=0.694, 95%CI: 0.482-0.906, P < 0.01). In the hematoxylin-eosin sections obtained from 80 patients, BRAF V600E was still the main type of gene mutation, and the classical/follicular type was more distributed. TERT promotor and RET/PTC1 mutation were the main genetic events for tall-cell/columnar/hobnail type and diffuse sclerosing type, respectively. One-way ANOVA showed that there were differences in diagnosis age(P=0.029) and tumor size(P < 0.01) among different pathological types.Conclusion As a simple and feasible clinical detection method for PTC, the multigene assay can supplement the identification of important genetic events other than BRAF V600E, and provide more prognostic information and follow-up hints for postoperative patients.
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表 1 基因突变及未突变组临床资料比较
BRAF
阴性
(n=29)BRAF
阳性
(n=132)P TERTp
阴性
(n=154)TERTp
阳性
(n=7)P RET/PTC1
阴性
(n=144)RET/PTC1
阳性
(n=10)P 一般资料 女/男/例 26/3 91/41 0.023 111/43 6/1 0.675 102/42 9/1 0.346 年龄/岁 41.0±14.2 42.6±12.8 0.561 42.1±13.0 46.7±12.5 0.361 42.4±12.9 38.5±15.6 0.367 家族史/例 0 12 0.126 12 0 1.000 12 0 1.000 恶性肿瘤病史/例 0 5 0.586 5 0 1.000 5 0 1.000 肿瘤体积 肿瘤最大径/cm 1.0±0.7 1.1±0.7 0.482 1.1±0.7 1.7±1.0 0.019 1.1±0.7 0.9±0.5 0.459 微小癌(最大径≤1 cm)/例(%) 19(65.5) 77(58.3) 0.475 94(61.0) 2(28.6) 0.187 88(61.1) 7(70.0) 0.824 病理特征/例(%) 多灶 6(20.7) 50(37.9) 0.078 51(33.1) 5(71.4) 0.050 49(34.0) 2(20.0) 0.342 腺体外侵犯 4(13.8) 18(13.7) 1.000 20(13.1) 2(28.6) 0.247 20(13.9) 0(0.0) 0.437 淋巴结分期/例(%) N0 10(34.5) 64(48.5) 0.188 73(47.4) 1(14.3) 0.031 70(48.6) 3(30.0) 0.198 N1a 7(24.1) 35(26.5) 41(26.6) 1(14.3) 39(27.1) 2(20.0) N1b 12(41.4) 33(25.0) 40(26.0) 5(71.4) 35(24.3) 5(50.0) 合并桥本甲状腺炎/例(%) 23(79.3) 44(33.3) < 0.001 67(43.5) 0(0.0) 0.042 57(39.6) 10(100.0) < 0.001 
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表 2 不同病理亚型间临床资料比较
滤泡或经典型 高细胞/柱状/靴钉型 弥漫硬化型 F P 突变事件/例 BRAF (n=67) 39 16 12 - - TERTp (n=3) 1 2 0 - - RAS (n=1) 0 0 1 - - RET/PTC1 (n=5) 2 0 3 - - 无(n=8) 7 1 0 - - 临床特征 年龄/岁 43.9±13.7 39.6±12.8 33.9±8.1 3.707 0.029 肿瘤最大径/cm 1.0±0.6 1.8±0.7 1.6±0.5 14.485 < 0.001 多灶/例(%) 20(41.7) 5(29.4) 6(40.0) - 0.668 腺体外侵犯/例(%) 9(18.8) 3(17.6) 3(20.0) - 0.986 颈侧区淋巴结转移/例(%) 10(20.8) 7(41.2) 9(60.0) - 0.013
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| 引用本文: |
史苑, 钱凯, 郭凯, 等. 甲状腺乳头状癌多基因检测与临床特征分析[J]. 临床耳鼻咽喉头颈外科杂志, 2023, 37(5): 375-379. doi: 10.13201/j.issn.2096-7993.2023.05.011
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| Citation: |
SHI Yuan, QIAN Kai, GUO Kai, et al. Clinical significance of multigene assay in papillary thyroid carcinoma[J]. J Clin Otorhinolaryngol Head Neck Surg, 2023, 37(5): 375-379. doi: 10.13201/j.issn.2096-7993.2023.05.011
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