RET原癌基因p．C618Y突变的家族性甲状腺髓样癌一家系的临床诊治分析  

Clinical diagnosis and treatment of familial medullary thyriod carcinoma caused by a p. C618Y RETproto-oncogene mutation in a Chinese pedigree

作　　者：赵坚强[1] 郭良[1] 戚晓平[2] 陈振光[2] 王可敬[1] 楼建林[1] 余秀华[3] 成军[3] 金杭阳[2] 李小龙[2] 应荣彪 张成宁[5] 

机构地区：[1]浙江省肿瘤医院头颈外科,杭州310022 [2]解放军第一一七医院肿瘤泌尿外科 [3]解放军第一一七医院肿瘤超声科 [4]浙江省台州市肿瘤医院肿瘤外科 [5]浙江大学医学院生化和遗传学系细胞生物研究所

出　　处：《中华医学杂志》2013年第6期440-444,共5页National Medical Journal of China

基　　金：南京军区医学科技创新课题基金重点项目（092038、102036）

摘　　要：目的探讨家族性甲状腺髓样癌（FMTC）的临床诊治特点及RET原癌基因检测的意义。方法对1个FMTC家系进行系统的家系调查，提取外周血进行RET原癌基因和降钙素检测，并绘制家系图。结果基因检测该家系为RET原癌基因第10外显子第618位点TGC→4TAC杂合错义突变，即P．C618Y突变，与临床完全符合。7例MTC中，男1例，女6例；首次诊断平均年龄49．6（24-78）岁；临床均表现为颈部肿块；肿瘤最大直径1．4-4．4cm，平均2．6cm；7例均伴颈部淋巴结转移。除1例（78岁）拒绝手术外，1例行右侧甲状腺全切除术＋左侧甲状腺次全切除术，1例行右侧甲状腺全切除术（既往左侧甲状腺因“良性肿瘤”已全切除），其余4例行双侧甲状腺全切除术；6例均＋至少双侧颈部Ⅵ区淋巴结清扫或＋单／双侧颈部改良淋巴结清扫术。接受手术的6例患者首次术后降钙素仍升高：其中1例首次术后64个月因MTC转移死亡；3例在首次术后6个月行再次手术，2例降钙素降至正常，1例降钙素仍升高；另外2例分别在首次术后214、60个月，影像学检查示双侧甲状腺叶残留、局部淋巴结肿大并降钙素升高。2例无症状中的1例因术前血清降钙素高，行双侧甲状腺全切除术，术后病理诊断为双侧甲状腺C细胞增生；另1例已随访10个月，未发现影像学和降钙素异常。结论基于家系调查并整合RET基因和降钙素检测，有利于早期诊断以改善预后；对无症状的RET基因突变携带者，应根据其降钙素水平，实施个体化的预防性甲状腺全切除或严密随访观察。diameter of MTC was 2. 6 cm （ range 1.4 - 4. 4）. Seven patients underwent thyroidectomy except a 78-year- old female patient： right total and left subtotal thyroidectomy （ n = 1 ）, right total thyroidectomy （ previous left total thyroidectomy for benign mass） （ n = l ） and total thyroidectomy （ n = 4） were performed. All procedures were accompanied by at least bilateral level VI lymph node dissection and/or with modified single/bilateral neck dissection. After the first operation, 6 patients still presented a high value of calcitonin： 1 patient died of metastasis 64 months postoperatively; 3 patients underwent reoperation at 6 months after initial operation, the calcitonin levels dropped to normal in 2/3 cases and stayed higher in 1 case; another two cases presented bilateral thyroid gland residua, local lymph node enlargement on imaging examination and elevated levels of calcitonin at 214 and 60 months postoperation respectively. However, 1/ 2 asymptomatic with elevated pre-operative calcitonin subjects underwent total thyroidectomy and histopathological examination showed bilateral C cell hyperplasia. The other carriers, without surgery, with normal neck images, close monitoring and a 10-month follow-up, still presented undetectable calcitonin. Conclusions Based on family survey, integrated RET screening and serum levels of calcitonin facilitate an early diagnosis and normalize surgery to improve the prognosis. For asymptomatic RET mutation carriers, their levels of calcitonin shall guide the individualized regimen of prophylactic thyroidectomy or strict monitoring and follow-ups.

关 键 词：多发性内分泌瘤病 癌 髓样 系谱 RET原癌基因 点突变 

分 类 号：R736.1[医药卫生—肿瘤]