细针穿刺检测BRAFV600E突变丰度与甲状腺乳头状癌临床病理特征的相关性

Correlation between the preoperative abundance of fine-needle aspiration (FNA)-BRAFV600E mutations and clinicopathological features of papillary thyroid carcinoma

摘要:

目的 探讨术前细针穿刺基因检测BRAF^V600E突变丰度与甲状腺乳头状癌（papillary thyroid cancer，PTC）临床病理特征的关系。方法 回顾性统计2021年1月30日至2022年2月28日就诊于南京中医药大学附属中西医结合医院的301例患者临床资料，术前细针穿刺基因检测示BRAF^V600E突变（含突变丰度检测），所有患者完成甲状腺癌根治术，术后病理证实为甲状腺乳头状癌，分析BRAF^V600E基因突变丰度与临床病理特征的关系。结果 纳入301例患者，男91例，女210例，年龄42（33~51）岁，范围18~69岁。肿瘤直径>1 cm的患者BRAF^V600E基因突变丰度高于肿瘤直径≤1 cm者［29.05（18.03~37.56） vs. 18.35（6.74~29.61），P<0.001］，颈部淋巴结转移患者BRAF^V600E基因突变丰度高于无颈部淋巴结转移者［24.72（8.08~34.32） vs. 18（8.68~28.54），P=0.040］。男女分开统计，女性颈部淋巴结转移患者BRAF^V600E基因突变丰度高于无颈部淋巴结转移者［25.75（9.62~34.30） vs. 17.47（7.27~26.86），P=0.007］，男性患者BRAF^V600E基因突变丰度与颈部淋巴结转移无明显相关性（P=0.654）。通过受试者工作特征（receiver operating characteristic，ROC）曲线分析BRAF^V600E突变丰度诊断女性PTC患者颈部淋巴结转移的效能，曲线下面积（area under the curve，AUC）为0.609（95%CI=0.532~0.686），取截断值25.68%。多因素分析显示，年龄<55岁（OR=0.138~0.735，P=0.007）、BRAF^V600E突变丰度≥25.68%（OR=1.271~4.65，P=0.007）、多灶（OR=1.282~4.623，P=0.007）、肿瘤直径>1 cm（OR=2.257~11.927，P<0.001）与女性PTC患者颈部淋巴结转移有明显相关性（P<0.05）。结论 BRAF^V600E突变丰度与PTC患者肿瘤直径、颈部淋巴结转移明显相关。BRAF^V600E突变丰度≥25.68%的女性PTC患者颈部淋巴结转移率明显升高。

Abstract:

Objective To investigate the relationship between the preoperative abundance of fine-needle aspiration（FNA）-BRAF^V600E mutations and clinicopathological features of papillary thyroid cancer（PTC）.Methods Retrospective analysis was performed on the clinical data of 301 patients who underwent radical thyroidectomy in Affiliated Hospital of Integrated Traditional Chinese and Western Medicine of Nanjing University of Chinese Medicine from January 30，2021 to February 28，2022. Preoperative FNA of all patients showed BRAF^V600E mutation. All patients underwent preoperative mutant abundance detection， and PTC was confirmed by postoperative pathology analysis. The relationship between BRAF^V600E mutant abundance and clinicopathological features was analyzed.Results A total of 301 patients were enrolled，including 91 males and 210 females. The median age of the patients was 42（33-51） years old， ranging from 18 to 69 years old. The abundance of BRAF^V600E mutation in patients with tumor diameter more than 1 cm was higher than that in patients with tumor diameter no more than 1 cm［29.05（18.03-37.56） vs. 18.35（6.74-29.61），P<0.001］. The abundance of BRAF^V600E mutation in patients with cervical lymph node metastasis was higher than that in patients without cervical lymph node metastasis［24.72（8.08-34.32） vs. 18（8.68-28.54），P=0.040］. The abundance of BRAF^V600E mutation in female patients with cervical lymph node metastasis was higher than that in patients without cervical lymph node metastasis［25.75（9.62-34.30） vs. 17.47（7.27-26.86），P=0.007］，but there was no statistical significance among male patients（P=0.654）. The receiver operating characteristic（ROC） curve for predicting cervical lymph node metastasis in female PTC patients was constructed with the abundance of BRAF^V600E mutation（AUC=0.609，95%CI=0.532-0.686），and the cutoff value was 25.65%. Multivariate analysis showed that the following aspects had a significant correlation with cervical lymph node metastasis in female PTC patients（P<0.05），such as less than 55 years old（OR=0.138-0.735，P=0.007），BRAF^V600E mutant abundance no less than 25.68%（OR=1.271-4.65，P=0.007），multifocality（OR=1.282-4.623，P=0.007） and tumor diameter more than 1 cm（OR=2.257-11.927，P<0.001）.Conclusion The abundance of BRAF^V600E mutation was significantly correlated with tumor diameter and cervical lymph node metastasis in PTC patients. The rate of cervical lymph node metastasis of female PTC patients with BRAF^V600E mutant abundance of no less than 25.68% has been significantly increased.