Prophylactic thyroidectomy for MEN 2-related medullary thyroid carcinoma based on predictive testing for RET proto-oncogene mutation and basal serum calcitonin in China

• Published in: European journal of surgical oncology Vol. 39; no. 9; pp. 1007 - 1012
• Main Authors: Qi, X-P, Zhao, J-Q, Du, Z-F, Yang, R-R, Ma, J-M, Fei, J, Cheng, J, Han, J-S, Jin, H-Y, Chen, Z-G, Wang, J-Q, Yang, Y-P, Ying, R-B, Chen, X-L, Liu, W-T, Zhao, Y, Jiang, H-L, Zhang, X-N
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-09-2013
• Subjects: Adolescent; Adult; Asian Continental Ancestry Group; Asymptomatic Diseases; Calcitonin - blood; Carcinoma, Medullary - congenital; Carcinoma, Medullary - diagnosis; Carcinoma, Medullary - prevention & control; Carcinoma, Medullary - surgery; Child; Child, Preschool; China; Female; Fully-automated chemiluminescence immunoassay; Hematology, Oncology and Palliative Medicine; Humans; Male; Medullary thyroid carcinoma; Middle Aged; Multiple Endocrine Neoplasia Type 2a - diagnosis; Multiple Endocrine Neoplasia Type 2a - genetics; Multiple Endocrine Neoplasia Type 2a - prevention & control; Multiple Endocrine Neoplasia Type 2a - surgery; Mutation; Mutation screening; Neck Dissection; Prophylactic thyroidectomy; Proto-Oncogene Proteins c-ret - genetics; RET; Serum calcitonin; Surgery; Thyroid Neoplasms - diagnosis; Thyroid Neoplasms - prevention & control; Thyroid Neoplasms - surgery; Thyroidectomy - methods; Young Adult; China; RET; Prophylactic thyroidectomy; Fully-automated chemiluminescence immunoassay; Mutation screening; Medullary thyroid carcinoma; Serum calcitonin
• ISSN: 0748-7983; 1532-2157
• DOI: 10.1016/j.ejso.2013.06.015

Abstract Introduction Early and normative surgery is the only curative method for multiple endocrine neoplasia type 2 (MEN 2)-related medullary thyroid carcinoma (MTC). Aims 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.