携带ret原癌基因804密码子变异的男性-2患者甲状腺髓样癌的自然史：法国神经内分泌肿瘤组（gte）的一项研究。

IF 2.9 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Annales d'endocrinologie Pub Date : 2025-01-20 DOI:10.1016/j.ando.2025.101705

Valentine Suteau , Maÿlis Lebeault , Martin Schlumberger , Mohamed Zalzali , Hélène Lasolle , Maëlle Le Bras , Gérard Chabrier , Isabelle Raingeard , Frédéric Castinetti , Philippe Caron , Cécile Ghander , Nicolas Chevalier , Delphine Mirebeau-Prunier , Vincent Rohmer , Patrice Rodien , Claire Briet

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引用次数: 0

摘要

背景：影响密码子804的RET变异是ATA分类中低风险组的一部分，5岁以上的适应症需要预防性甲状腺切除术。然而，攻击性似乎是可变的。本研究的目的是报道RET原癌基因密码子804处致病性变异的一大群法国携带者。方法：从法国GTE-ENDOCAN-RENATEN数据库中招募了来自12所大学医院的RET 804变异患者进行这项回顾性非介入性研究。评估甲状腺髓样癌（MTC）的发病率和严重程度（TNM分期和降钙素水平）、表型-基因型相关性和临床结果。结果：共分析322例患者。指标病例（n=65）诊断时的中位年龄为57岁（范围，46-66），亲属（n= 257）的中位年龄为37岁（范围，18-51）。指标病例首次降钙素测定中位数为240 ng/l（范围79- 1344），亲属降钙素测定中位数为6.7ng/l（范围0-22）。在指标病例中，致病性变异C . 2410g >A （p.Val804Met）在RET中的发生率（80%）高于C . 2410g >C或C . 2410g >T （p.Val804Leu）。MTC多灶性、淋巴结阳性和转移性分别为64%、51%和20%。TNM分期、术前降钙素水平和男性性别可预测持续性疾病（以术后降钙素>5ng/L定义）。结论：影响804密码子的RET致病变异主要导致疾病侵袭性低，出现时间晚，生存期延长。如果降钙素值高于6ng /l，我们建议对亲属进行手术，而不是10ng/l。长期观察是必须的，因为手术后几年仍有可能复发。

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Natural history of medullary thyroid carcinoma in MEN 2 patients carrying a variant at codon 804 in the RET proto-oncogene: A study by the French Neuroendocrine Tumor Group (GTE)

Background

RET variants affecting codon 804 are part of the low-to-moderate risk group in the ATA classification, with indications for prophylactic thyroidectomy beyond age of 5 years. However, aggressiveness seems to be variable. The objective of this study was to report a large cohort of French carriers of a pathogenic variant at codon 804 in the RET proto-oncogene.

Methods

Patients from 12 university hospitals with a RET 804 variant were recruited in this retrospective non-interventional French national study, from the French GTE-ENDOCAN-RENATEN database. Incidence and severity (TNM stage and calcitonin levels) of medullary thyroid carcinoma (MTC), phenotype-genotype correlation and clinical outcome were assessed.

Results

A total of 322 patients were analyzed. Index cases (n = 65) had a median age at diagnosis of 57 years (range: 46–66), and relatives (n = 257) a median age of 37 years (range: 18–51). Median first calcitonin measurement was 240 ng/L (range: 79–1344) in index cases, and 6.7 ng/L (range: 0–22) in relatives. In index cases, the pathogenic variant c.2410G>A (p.Val804Met) in RET was more frequent (80% of cases) than c.2410G>C or c.2410G>T (p.Val804Leu). MTC was multifocal, node-positive and metastatic in 64%, 51% and 20% of cases respectively. TNM stage, preoperative calcitonin level and male gender were predictive of persistent disease (defined by postoperative calcitonin > 5 ng/L) (P < 0.001). Ten-year disease-free survival (DFS) was 61%. In total, 113 relatives were operated on: 62% with MTC and 34% with isolated C-cell hyperplasia (CCH); the youngest patients were aged 20 for MTC and 4 years for CCH. Ten-year DFS was 90%.

Conclusion

The RET pathogenic variants affecting the codon 804 mainly led to low aggressiveness disease, with late presentation and prolonged DFS. We suggest surgery in relatives if calcitonin values are above 6 ng/L, instead of 10 ng/L. Long-term surveillance is mandatory, since recurrence remains possible several years after surgery.

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来源期刊

Annales d'endocrinologie 医学-内分泌学与代谢

CiteScore

4.40

自引率

6.50%

发文量

311

审稿时长

50 days

期刊介绍： The Annales d''Endocrinologie, mouthpiece of the French Society of Endocrinology (SFE), publishes reviews, articles and case reports coming from clinical, therapeutic and fundamental research in endocrinology and metabolic diseases. Every year, it carries a position paper by a work-group of French-language endocrinologists, on an endocrine pathology chosen by the Society''s Scientific Committee. The journal is also the organ of the Society''s annual Congress, publishing a summary of the symposia, presentations and posters. "Les Must de l''Endocrinologie" is a special booklet brought out for the Congress, with summary articles that are always very well received. And finally, we publish the high-level instructional courses delivered during the Henri-Pierre Klotz International Endocrinology Days. The Annales is a window on the world, keeping alert clinicians up to date on what is going on in diagnosis and treatment in all the areas of our specialty.