Association between RET genotype and disease phenotype in patients with hereditary medullary thyroid carcinoma

Abstract

Abstract:ObjectiveTo investigate the association between RET genotype and disease phenotype in the patients with hereditary medullary thyroid carcinoma (HMTC).MethodsA total of 13 patients diagnosed as HMTC and undergoing surgical treatment for thyroid carcinoma in this hospital from March 2015 to September 2019 were analyzed retrospectively with follow-up cutoff at September 2021. The patient risk stratification was performed according to American Thyroid Association (ATA) guidelines. The association between RET genotype and disease phenotype including biochemical results, TNM stage, both biochemical [normal serum calcitonin(CT)] cure and clinical cure was analyzed.ResultsThere were 1 (7.69%) case, 6(46.15%) cases, and 6(46.15%) cases with the highest risk mutation (RET M918T), high-risk mutation (RET C634Y and C634S), and moderate-risk mutation (RET C618G and C611Y), respectively. One case with the highest risk mutation was at TNM stage Ⅳ. There were 4 cases (66.67%) at stageⅠand 2 cases (33.33%) at stage Ⅲ among 6 cases with high-risk mutation. For 6 cases with moderate-risk mutation, stage Ⅰ and stage Ⅱ had 1 case(16.67%) respectively, and stage Ⅲ and stage Ⅳ with 3 cases (50%) and 1 case (16.67%) respectively. The highest preoperative CT and carcinoembryonic antigen were detected in 1 case with highest risk mutations (20 000 ng/L, 831.8 μg/L), and those lower in 6 cases with moderate-risk mutations (1 221.4 ng/L, 62.3 μg/L). The lowest of them were in 6 cases with high-risk mutations (537.7 ng/L, 41.7 μg/L). Similarly, both clinical cure rate and biochemical cure rate were found poorer in the cases with the highest risk mutation, and better in the case with high-risk mutation, and less better in the cases with moderate-risk mutation.ConclusionsRET gene could be associated with HMTC risk of ATA. The patients of RET genotype with high-risk mutations would have higher clinical cure rate and biochemical cure rate than the cases with moderate-risk mutations.

Key words:Medullary thyroid carcinoma,Hereditary medullary thyroid carcinoma,Multiple endocrine neoplasia syndrome,RET gene

CLC Number:

R736.1

ZHANG Gang, ZHANG Zhe, ZHANG Shu, LI Zhirong, TIAN Wuguo, HUANG Qi, WANG Lingli, XU Yan. Association between RET genotype and disease phenotype in patients with hereditary medullary thyroid carcinoma[J]. Journal of Surgery Concepts & Practice, 2021, 26(06): 522-527.

Figures/Tables4

临床信息	病例数（%）
年龄（岁）	39.5±13.2
性别
男	4（30.7）
女	9（69.3）
首诊症状
颈部包块	7（53.8）
体检发现CEA异常升高	2（15.4）
头痛、头晕	4（30.8）
肿瘤平均最大径（mm）	25.8±10.8
TNM分期
Ⅰ	5（38.5）
Ⅱ	1（7.7）
Ⅲ	6（46.1）
Ⅳ	1（7.7%）
手术范围
甲状腺全切除术	3（23.0）
甲状腺全切除术+双侧颈部中央区淋巴结清扫术	9（69.3）
甲状腺全切术+双侧颈部中央区淋巴结清扫术+颈侧区淋巴结清扫术	1（7.7）
肾上腺处理情况
双侧肾上腺嗜铬细胞瘤切除术	3（23）
单侧肾上腺嗜铬细胞瘤切除术	4（30.8）
单侧肾上腺内支增粗未行手术	2（15.4）
合并甲状旁腺增生	1（7.7）
MEN2分型
MEN2A	7（53.8）
MEN2B	1（7.7）
FMTC	5（35.5）
术后并发症
一过性甲状旁腺功能减退	10（71.2）
永久性甲状旁腺功能减退	2（15.4）

ATA风险类别	密码子（外显子）	病例数	百分比（%）
最高风险	M918T(16)	1	7.7
高风险	C634Y(11)	4	30.8
	C634S(11)	2	15.4
中风险	C611Y(10)	5	38.4
	C618G(10)	1	7.7

	最高风险（n=1）	高风险（n=6）	中风险（n=6）
男性（%）	0	66.7	0
初诊平均年龄（岁）	22.0	40.5	41.3
基础CT含量（0~18 ng/L）	20 000.0	537.7	1 221.4
基础CEA含量（0~5 μg/L）	831.8	41.7	62.3
TNM分期
Ⅰ	0	4	1
Ⅱ	0	0	1
Ⅲ	0	2	3
Ⅳ	1	0	1
临床治愈^a)	0	83.3%	66.7%
生化治愈^b)	0	83.3%	33.3%
手术方式
甲状腺全切除术	1	1	2
甲状腺全切除术+双侧颈部中央区淋巴结清扫除术	0	5	3
甲状腺全切除术+双侧颈部中央区淋巴结清扫术+颈侧区淋巴结清扫术	0	0	1

家系（n=10）	疾病表型	基因表型（RET 突变位点）	携带RET基因胚系突变（n）	携带RET基因胚系突变未患病或未行MTC手术（n）	诊断MTC（n）	诊断嗜铬细胞瘤（n）
1	MEN2B	M918T	2	1	1	1
2，3	MEN2A	C634Y	5	1	4	2
4	MEN2A	C634S	3	2	1	2^b）
5	FMTC	C634S	1	0	1	0
6	FMTC	C618G	1	0	1	0
7	MEN2A	C611Y	3	1	2	2
8，9，10	FMTC	C611Y	4	1	3	0

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