Uno Daisuke, Endo Kazuhira, Yoshikawa Tomomi, Hirai Nobuyuki, Kobayashi Eiji, Nakanishi Yosuke, Kondo Satoru, Yoshizaki Tomokazu
Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
Thyroid Res. 2024 Sep 16;17(1):21. doi: 10.1186/s13044-024-00209-4.
Activation of the MAPK pathway by genetic mutations (such as BRAF and RET) initiates and accelerates the growth of papillary thyroid carcinoma (PTC). However, the correlation between genetic mutations and clinical features remains to be established. Therefore, this study aimed to retrospectively analyze major genetic mutations, specifically BRAF mutations and RET rearrangements, and develop a treatment algorithm by comparing background and clinical characteristics.
One hundred thirteen patients with primary PTC were included in this study. BRAF mutations were detected via Sanger sequencing and RET rearrangements were detected via fluorescence in situ hybridization (FISH) analysis, and reverse transcription polymerase chain reaction (RT-PCR). The patients were categorized into two groups based on the presence of BRAF mutations and RET rearrangements and their clinical characteristics (age, sex, TNM, stage, extratumoral extension, tumor size, unifocal/multifocal lesions, vascular invasion, differentiation, chronic thyroiditis, preoperative serum thyroglobulin level, and F-fluorodeoxyglucose (FDG) uptake) were compared subsequently.
After excluding unanalyzable specimens, 80 PTC patients (22 males and 58 females, mean age: 57.2 years) were included in the study. RET rearrangements were positive in 8 cases (10%), and BRAF mutation was positive in 63 (78.6%). The RET rearrangement group was significantly associated with younger age (p = 0.024), multifocal lesion (p = 0.048), distant metastasis (p = 0.025) and decreased F-fluorodeoxyglucose uptake (p < 0.001). The BRAF mutation group was significantly associated with unifocal lesions (p = 0.02) and increased F-FDG uptake (p = 0.004).
In this study, an increase in M classification cases was found in the RET rearrangements group. However, genetic mutations were not associated with the clinical stage, and no factors that could be incorporated into the treatment algorithm were identified.
基因变异（如BRAF和RET）激活丝裂原活化蛋白激酶（MAPK）信号通路，启动并加速甲状腺乳头状癌（PTC）的生长。然而，基因变异与临床特征之间的相关性仍有待确定。因此，本研究旨在回顾性分析主要基因变异，特别是BRAF变异和RET重排，并通过比较背景和临床特征制定治疗方案。
本研究纳入113例原发性PTC患者。通过桑格测序检测BRAF变异，通过荧光原位杂交（FISH）分析和逆转录聚合酶链反应（RT-PCR）检测RET重排。根据BRAF变异和RET重排情况将患者分为两组，随后比较其临床特征（年龄、性别、TNM分期、肿瘤外侵犯、肿瘤大小、单灶/多灶性病变、血管侵犯、分化程度、慢性甲状腺炎、术前血清甲状腺球蛋白水平和氟脱氧葡萄糖（FDG）摄取情况）。
排除无法分析的标本后，本研究纳入80例PTC患者（22例男性和58例女性，平均年龄：57.2岁）。8例（10%）RET重排呈阳性，63例（78.6%）BRAF变异呈阳性。RET重排组与较年轻的年龄（p = 0.024）、多灶性病变（p = 0.048）、远处转移（p = 0.025）和氟脱氧葡萄糖摄取减少（p < 0.001）显著相关。BRAF变异组与单灶性病变（p = 0.02）和F-FDG摄取增加（p = 0.004）显著相关。
在本研究中，RET重排组中M分期病例增加。然而，基因变异与临床分期无关，未发现可纳入治疗方案的因素。
