Section of Endocrine Surgery, Department of General, Visceral and Transplantation Surgery, University Medical Centre, Johannes Gutenberg University Mainz, Mainz, Germany.
Institute of Pathology, University Medical Centre, Johannes Gutenberg-University Mainz, Mainz, Germany.
BJS Open. 2023 May 5;7(3). doi: 10.1093/bjsopen/zrad029.
Currently, treatment recommendations for papillary thyroid carcinoma are not based on the genetic background causing tumourigenesis. The aim of the present study was to correlate the mutational profile of papillary thyroid carcinoma with clinical parameters of tumour aggressiveness, to establish recommendations for risk-stratified surgical treatment.
Papillary thyroid carcinoma tumour tissue of patients undergoing thyroid surgery at the University Medical Centre Mainz underwent analysis of BRAF, TERT promoter and RAS mutational status as well as potential RET and NTRK rearrangements. Mutation status was correlated with clinical course of disease.
One hundred and seventy-one patients operated for papillary thyroid carcinoma were included. The median age was 48 years (range 8-85) and 69 per cent (118/171) of patients were females. One hundred and nine papillary thyroid carcinomas were BRAF-V600E mutant, 16 TERT promotor mutant and 12 RAS mutant; 12 papillary thyroid carcinomas harboured RET rearrangements and two papillary thyroid carcinomas showed NTRK rearrangements. TERT promoter mutant papillary thyroid carcinomas had a higher risk of distant metastasis (OR 51.3, 7.0 to 1048.2, P < 0.001) and radioiodine-refractory disease (OR 37.8, 9.9 to 169.5, P < 0.001). Concomitant BRAF and TERT promoter mutations increased the risk of radioiodine-refractory disease in papillary thyroid carcinoma (OR 21.7, 5.6 to 88.9, P < 0.001). RET rearrangements were associated with a higher count of tumour-affected lymph nodes (OR 7950.9, 233.7 to 270495.7, P < 0.001) but did not influence distant metastasis or radioiodine-refractory disease.
Papillary thyroid carcinoma with concomitant BRAF-V600E and TERT promoter mutations demonstrated an aggressive course of disease, suggesting the need for a more extensive surgical strategy. RET rearrangement-positive papillary thyroid carcinoma did not affect the clinical outcome, potentially obviating the need for prophylactic lymphadenectomy.
目前，针对甲状腺乳头状癌的治疗建议并非基于导致肿瘤发生的遗传背景。本研究旨在分析甲状腺乳头状癌的突变特征与肿瘤侵袭性的临床参数的相关性，为风险分层手术治疗提供建议。
对在美因茨大学医学中心接受甲状腺手术的甲状腺乳头状癌患者的肿瘤组织进行 BRAF、TERT 启动子和 RAS 突变状态以及潜在的 RET 和 NTRK 重排分析。对突变状态与疾病的临床过程进行相关性分析。
共纳入 171 例因甲状腺乳头状癌接受手术的患者。患者的中位年龄为 48 岁（8-85 岁），69%（118/171）为女性。109 例甲状腺乳头状癌为 BRAF-V600E 突变，16 例为 TERT 启动子突变，12 例为 RAS 突变；12 例甲状腺乳头状癌存在 RET 重排，2 例存在 NTRK 重排。TERT 启动子突变的甲状腺乳头状癌发生远处转移的风险更高（OR 51.3，7.0 至 1048.2，P＜0.001）和放射性碘难治性疾病（OR 37.8，9.9 至 169.5，P＜0.001）的风险更高。BRAF 和 TERT 启动子同时突变会增加甲状腺乳头状癌放射性碘难治性疾病的风险（OR 21.7，5.6 至 88.9，P＜0.001）。RET 重排与更多受肿瘤影响的淋巴结数量相关（OR 7950.9，233.7 至 270495.7，P＜0.001），但不影响远处转移或放射性碘难治性疾病。
同时存在 BRAF-V600E 和 TERT 启动子突变的甲状腺乳头状癌表现出侵袭性疾病过程，表明需要更广泛的手术策略。RET 重排阳性的甲状腺乳头状癌不会影响临床结局，可能无需预防性淋巴结切除术。
