title: Prophylactic thyroidectomy for MEN 2-related medullary thyroid carcinoma based on predictive testing for RET proto-oncogene mutation and basal serum calcitonin in China.
abstract: BACKGROUND
  Early and normative surgery is the only curative method for multiple endocrine neoplasia type 2 (MEN 2)-related medullary thyroid carcinoma (MTC).
  
  
  OBJECTIVE
  To study the timing of prophylactic total thyroidectomy (TT) for MEN 2-related MTC with different RET mutations in a Chinese population, and to compare the sensitivity and accuracy of fully-automated chemiluminescence immunoassay (FACLIA) and radioimmunoassay (RIA) for serum calcitonin (Ct).
  
  
  METHODS
  We collected 24 asymptomatic individuals from 8 unrelated Chinese families with MEN 2, and analyzed RET mutation and Ct levels. Then we performed TT on 17 of the 24 individuals, including TT (2/17), TT with bilateral level VI lymph-node dissection (B-LND(VI); 12/17) and TT with B-LND(VI) + modified unilateral/bilateral/local neck dissection (3/17).
  
  
  RESULTS
  Histopathology revealed bilateral/unilateral MTC in 15/17 (88.2%; median diameter, 1.0 cm) and bilateral C-cell hyperplasia in 2/17 (11.8%; p.V292M/R67H/R982C and p.C618Y). Lymph-node metastasis/fibro-adipose tissue invasion (p.C634R) or solely fibro-adipose tissue invasion (p.C634Y) were found in 2/17 (11.8%). Elevated pre-surgical Ct (pre-Ct) was identified by FACLIA in 17/17 (median age, 24.0), while pre-Ct by RIA was found in only 6/15 (P < 0.001). The median follow-up was 22.0 months, during which 16/17 had no abnormality (one p.C634R individual had elevated Ct), and another 7 carriers still had consistently undetectable Ct by FACLIA.
  
  
  CONCLUSIONS
  Our study highlights the importance and feasibility of individualized prophylactic TT for MEN 2-related MTC, based on predictive integrated screening of RET and pre-Ct levels. Besides, we recommend FACLIA to measure Ct for earlier diagnosis, treatment and follow-up monitoring of MTC.
authors.affiliation: Department of Oncologic and Urologic Surgery, Clinical Experimental Center and Department of Pathology, The 117th PLA Hospital, 40 Jichang Road, Hangzhou, Zhejiang Province 310004, China. Electronic address: qxplmd@vip.sina.com.
authors.forename: X P
authors.initials: XP
authors.lastname: Qi
authors.forename: J Q
authors.initials: JQ
authors.lastname: Zhao
authors.forename: Z F
authors.initials: ZF
authors.lastname: Du
authors.forename: R R
authors.initials: RR
authors.lastname: Yang
authors.forename: J M
authors.initials: JM
authors.lastname: Ma
authors.forename: J
authors.initials: J
authors.lastname: Fei
authors.forename: J
authors.initials: J
authors.lastname: Cheng
authors.forename: J S
authors.initials: JS
authors.lastname: Han
authors.forename: H Y
authors.initials: HY
authors.lastname: Jin
authors.forename: Z G
authors.initials: ZG
authors.lastname: Chen
authors.forename: J Q
authors.initials: JQ
authors.lastname: Wang
authors.forename: Y P
authors.initials: YP
authors.lastname: Yang
authors.forename: R B
authors.initials: RB
authors.lastname: Ying
authors.forename: X L
authors.initials: XL
authors.lastname: Chen
authors.forename: W T
authors.initials: WT
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: H L
authors.initials: HL
authors.lastname: Jiang
authors.forename: X N
authors.initials: XN
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People; D058070:Asymptomatic Diseases; D002116:Calcitonin / Q000097:blood*; D018276:Carcinoma, Medullary / Q000151:congenital* / Q000175:diagnosis / Q000517:prevention & control / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D002681:China; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000175:diagnosis / Q000235:genetics / Q000517:prevention & control / Q000601:surgery*; D009154:Mutation; D037981:Neck Dissection; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000517:prevention & control / Q000601:surgery*; D013965:Thyroidectomy / Q000379:methods*; D055815:Young Adult
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D002116:Calcitonin; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human
keywords: Fully-automated chemiluminescence immunoassay; Medullary thyroid carcinoma; Mutation screening; Prophylactic thyroidectomy; RET; Serum calcitonin