Nhung Nguyen Thi, Hoang Van Dong, Mussazhanova Zhanna, Kurohama Hirokazu, Ha Le Ngoc, Matsuda Katsuya, Nguyen Van Phu Thang, Hanh Ngo Thi Minh, Nguyen Thi Ngoc Anh, Nakashima Masahiro
Endocr Connect. 2025 Jul 30;14(7). doi: 10.1530/EC-25-0116. Print 2025 Jul 1.
Papillary thyroid carcinoma (PTC) is the most prevalent histological subtype of thyroid cancer. However, it remains unclear whether BRAF V600E, TERT promoter (TERT-p), and certain pathological markers, such as loss of polarity/loss of cell cohesiveness (LOP/LCC), tall cells, mitotic count, and Ki-67 labeling index (LI) in recurrent tumors, are associated with clinical outcomes in patients with PTC after reoperation for recurrent PTC. This study investigates the impact of BRAF V600E and TERT-p mutations on progression-free survival (PFS) after reoperation for recurrent PTC. Cox regression analysis was employed to identify parameters associated with PFS. During a mean follow-up period of 27 months after reoperation, 39 patients (21.3%) experienced disease progression. Coexistence of BRAF V600E and TERT-p mutations (double mutation: Dmut) was observed in 21.3% of patients. TERT-p, Dmut, LOP/LCC (≥10%), mitotic count (≥3 per 2 mm2), and Ki-67 LI were found to be significantly associated with disease progression in unadjusted analyses. In a multivariable analysis, these associations remained significant, with hazard ratios and 95% confidence intervals for TERT-p, Dmut, LOP/LCC, mitotic count, and Ki-67 LI being 5.98 (2.31-15.5), 5.44 (2.21-13.3), 6.81 (2.00-23.2), 5.05 (2.07-12.3), and 5.85 (2.48-13.7), respectively. Extranodal extension was associated with disease progression in both unadjusted and multivariable analyses. TERT-p, Dmut, Ki-67 LI, LOP/LCC, mitotic count, and extranodal extension were identified as independent risk factors for poor PFS after reoperation. Close surveillance following reoperation is recommended for patients exhibiting these factors.
乳头状甲状腺癌（PTC）是甲状腺癌最常见的组织学亚型。然而，复发肿瘤中的BRAF V600E、端粒酶逆转录酶启动子（TERT-p）以及某些病理标志物，如极性丧失/细胞黏附丧失（LOP/LCC）、高细胞、有丝分裂计数和Ki-67标记指数（LI）是否与复发性PTC再次手术后患者的临床结局相关仍不清楚。本研究调查BRAF V600E和TERT-p突变对复发性PTC再次手术后无进展生存期（PFS）的影响。采用Cox回归分析确定与PFS相关的参数。在再次手术后平均27个月的随访期内，39例患者（21.3%）出现疾病进展。21.3%的患者观察到BRAF V600E和TERT-p突变共存（双突变：Dmut）。在未校正分析中，TERT-p、Dmut、LOP/LCC（≥10%）、有丝分裂计数（每2平方毫米≥3个）和Ki-67 LI被发现与疾病进展显著相关。在多变量分析中，这些关联仍然显著，TERT-p、Dmut、LOP/LCC、有丝分裂计数和Ki-67 LI的风险比和95%置信区间分别为5.98（2.31-15.5）、5.44（2.21-13.3）、6.81（2.00-23.2）、5.05（2.07-12.3）和5.85（2.48-13.7）。在未校正和多变量分析中，淋巴结外侵犯均与疾病进展相关。TERT-p、Dmut、Ki-67 LI、LOP/LCC、有丝分裂计数和淋巴结外侵犯被确定为再次手术后PFS不良的独立危险因素。建议对表现出这些因素的患者在再次手术后进行密切监测。
