Molecular diagnosis and comprehensive treatment of multiple endocrine neoplasia type 2 in Southeastern Chinese

Hereditary Cancer in Clinical Practice

Xiao-Ping Qi²  Zhen-Guang Chen²  Jian-Qiang Zhao¹ 

[1] Department of Head and Neck Surgery, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, China;Department of Oncologic and Urologic Surgery, the 117th PLA Hospital, Wenzhou Medical University, 40 Jichang Road, Hangzhou 310004, Zhejiang Province, China

关键词: Cortical-sparing adrenalectomy;    Prophylactic thyroidectomy;    RET;    Mutation screening;    Multiple endocrine neoplasia type 2;   

Others  :  1133769
DOI  :  10.1186/s13053-015-0026-1

 received in 2014-08-21, accepted in 2015-01-07,  发布年份 2015

【 摘 要 】

Background

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant inherited endocrine malignancy syndrome. Early and normative surgery is the only curative method for MEN 2-related medullary thyroid carcinoma (MTC). In patients with adrenal pheochromocytoma, cortical-sparing adrenalectomy (CSA) can be utilized to preserve adrenocortical function.

Methods

We present twenty-six of 33 MEN2 patients underwent prophylactic thyroidectomy with varying neck dissection and eight of 24 MEN2A patients with PHEO underwent adrenal-sparing surgery. Direct sequencing of entire RET exons was performed in all participants.

Results

The RET mutations (p.C634Y [n = 10], p.C634R [n = 9], p.C634F [n = 2], p.C618Y [n = 8], p.C618R [n = 3], and p.M918T [n = 1]) were confirmed in 20 symptomatic patients and identified in 13 at-risk relatives (RET carriers). Twenty-six of 33 MEN2 patients underwent thyroidectomies with neck dissections; the mean age at the time of the first thyroid surgery and the tumor diameter of the 6 RET carriers was decreased compared with 20 symptomatic patients (P < 0.001 and P = 0.007, respectively), while the disease-free survival was increased (80% vs.10%, P = 0.0001). Seven RET carriers who were declined surgery. One of 20 symptomatic patients with MTC bone metastases after surgery received vandetanib therapy for 20 months and responded well. Additionally, 8 of 24 MEN2A patients who initially had unilateral pheochromocytomas underwent CSA, 1 developed contralateral pheochromo cytomas 10 years later, then also accepted and also agreed to a CSA. None of the patients required steroid replacement therapy.

Conclusions

Based on our results, integrated RET screening and the pre-operative calcitonin level is an excellent strategy to ensure earlier diagnosis and standard thyroidectomy. CSA can be utilized to preserve adrenocortical function in patients with pheochromocytomas.

【 授权许可】

   
2015 Zhao et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

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