Journal List > Endocrinol Metab > v.25(3) > 1085826

Jang, Lee, Hur, Kim, Kim, Min, Lee, Lee, Kim, and Chung: Clinicopathological Characteristics and Prognostic Factors of Medullary Thyroid Carcinoma



Studies on the clinicopathological characteristics and prognostic factors of medullary thyroid carcinoma (MTC) in Korea are very rare.


We enrolled 56 MTC patients who underwent surgery at Samsung Medical Center from 1995 to 2006. We analyzed their gender, age at diagnosis, the pathologic findings, the TNM stage, the association with multiple endocrine neoplasia (MEN), RET protooncogene mutation and the, serum basal calcitonin levels before and after the surgery. We investigated the overall survival and the prognostic factors.


The mean age at diagnosis was 46 years and the male/female ratio was 1:2.7. Fine needle aspiration cytology detected 61% of the MTC. The mean tumor size was 2.6 cm (range: 0.2-9.0 cm). Fifty-two percent of patients had the TNM stage more than III at the time of diagnosis. Distant metastasis was found in 5.3% (3/56) of the patients, either at the time of diagnosis or during the follow-up period. Hereditary MTC comprised of 23% of the patients and the disease developed at a younger age (38 years vs. 48 years, respectively, P < 0.05) with more bilaterality. RET protooncogene mutations were found in 27% (9/33) of the patients and most of them were in codon 634. After the primary surgery, the serum basal calcitonin levels were persistently elevated over 13 ng/L in 49% of the patients. The overall 5-year survival rate was 95.5%. Tumor size and distant metastasis were the significant prognostic factors for survival by univariate analysis (P < 0.05).


There were no significant differences in the clinicopathological characteristics of MTC and survival in Korea compared to those of the Western countries.

Figures and Tables

Fig. 1
Changes of serum calcitonin levels before and after surgery. A. Patients with normalized serum calcitonin level after surgery. B. Patients with persistent hypercalcitoninemia after surgery. C. Patients who passed away during follow-up.
Fig. 2
Tumor size according to basal serum calcitonin levels.
Table 1
Diagnosis of medullary thyroid carcinoma

MEN, multiple endocrine neoplasia.

Table 2
Clinical characteristics of three medullary thyroid carcinoma patients with distant metastasis

*Detected at the time of diagnosis; alive.

ET, extrathyroidal; LN, lymph node.

Table 3
Clinicopathologic features of MTC patients

Values are expressed as mean ± standard deviation.

MTC, medullary thyroid carcinoma; NS, not significant.

Table 4
Analysis of RET mutations and clinical features in nine RET-positive patients with medullary thyroid carcinoma

*Tumor staging was evaluated using the pTNM staging system established by the American Joint Committee on Cancer; We defined remission as the normalization of the serum calcitonin concentration (less than 13 ng/L) with no evidence of residual tumor or metastasis, as determined by an imaging scan.

ACG (T), threonine; AGC (S), serine; ATG (M), methionine; CGC (R), arginine; GAC (D), aspartate; MEN, multiple endocrine neoplasia; TAC (Y), tyrosine; TGC (C), cysteine; TGG (W), tryptophan.

Table 5
Risk factors of persistent hypercalcitoninemia after surgery in univariate and multivariate analysis


1. Kebebew E, Ituarte PH, Siperstein AE, Duh QY, Clark OH. Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems. Cancer. 2000. 88:1139–1148.
2. Oh SK, Kim JS. Medullary carcinoma of the thyroid. J Korean Surg Soc. 1999. 56:49–58.
3. Yip L, Cote GJ, Shapiro SE, Ayers GD, Herzog CE, Sellin RV, Sherman SI, Gagel RF, Lee JE, Evans DB. Multiple endocrine neoplasia type 2: evaluation of the genotype-phenotype relationship. Arch Surg. 2003. 138:409–416.
4. Chung YJ, Kim HH, Kim HJ, Min YK, Lee MS, Lee MK, Kim KW, Ki CS, Kim JW, Chung JH. RET proto-oncogene mutations are restricted to codon 634 and 618 in Korean families with multiple endocrine neoplasia 2A. Thyroid. 2004. 14:813–818.
5. Gimm O, Sutter T, Dralle H. Diagnosis and therapy of sporadic and familial medullary thyroid carcinoma. J Cancer Res Clin Oncol. 2001. 127:156–165.
6. Bae SJ, Kim DJ, Kim JY, Park SY, Choi SH, Song YD, Ki CS, Chung JH. A rare extracellular D631Y germline mutation of the RET proto-oncogene in two Korean families with MEN2A. Thyroid. 2006. 16:609–614.
7. Eng C, Clayton D, Schuffenecker I, Lenoir G, Cote G, Gagel RF, van Amstel HK, Lips CJ, Nishisho I, Takai SI, Marsh DJ, Robinson BG, Frank-Raue K, Raue F, Xue F, Noll WW, Romei C, Pacini F, Fink M, Niederle B, Zedenius J, Nordenskjöld M, Komminoth P, Hendy GN, Mulligan LM, et al. The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis. JAMA. 1996. 276:1575–1579.
8. Kim HH, Kim HJ, Chung YJ, Min YK, Lee MS, Lee MK, Kim KW, Ki CS, Kim JW, Chung JH. Analysis of Ret proto-oncogene mutation in Korean patients with medullary thyroid carcinomas. J Korean Soc Endocrinol. 2003. 18:360–370.
9. Schuffenecker I, Virally-Monod M, Brohet R, Goldgar D, Conte-Devolx B, Leclerc L, Chabre O, Boneu A, Caron J, Houdent C, Modigliani E, Rohmer V, Schlumberger M, Eng C, Guillausseau PJ, Lenoir GM. Risk and penetrance of primary hyperparathyroidism in multiple endocrine neoplasia type 2A families with mutations at codon 634 of the RET proto-oncogene. Groupe D'etude des Tumeurs à Calcitonine. J Clin Endocrinol Metab. 1998. 83:487–491.
10. Bugalho MJ, Santos JR, Sobrinho L. Preoperative diagnosis of medullary thyroid carcinoma: fine needle aspiration cytology as compared with serum calcitonin measurement. J Surg Oncol. 2005. 91:56–60.
11. Brandi ML, Gagel RF, Angeli A, Bilezikian JP, Beck-Peccoz P, Bordi C, Conte-Devolx B, Falchetti A, Gheri RG, Libroia A, Lips CJ, Lombardi G, Mannelli M, Pacini F, Ponder BA, Raue F, Skogseid B, Tamburrano G, Thakker RV, Thompson NW, Tomassetti P, Tonelli F, Wells SA Jr, Marx SJ. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 2001. 86:5658–5671.
12. Hahm JR, Lee MS, Min YK, Lee MK, Kim KW, Nam SJ, Yang JH, Chung JH. Routine measurement of serum calcitonin is useful for early detection of medullary thyroid carcinoma in patients with nodular thyroid diseases. Thyroid. 2001. 11:73–80.
13. Cohen R, Campos JM, Salaun C, Heshmati HM, Kraimps JL, Proye C, Sarfati E, Henry JF, Niccoli-Sire P, Modigliani E. Preoperative calcitonin levels are predictive of tumor size and postoperative calcitonin normalization in medullary thyroid carcinoma. Groupe d'Etudes des Tumeurs a Calcitonine (GETC). J Clin Endocrinol Metab. 2000. 85:919–922.
14. Bockhorn M, Frilling A, Rewerk S, Liedke M, Dirsch O, Schmid KW, Broelsch CE. Lack of elevated serum carcinoembryonic antigen and calcitonin in medullary thyroid carcinoma. Thyroid. 2004. 14:468–470.
15. Sand M, Gelos M, Sand D, Bechara FG, Bonhag G, Welsing E, Mann B. Serum calcitonin negative medullary thyroid carcinoma. World J Surg Oncol. 2006. 4:97.
16. Modigliani E, Cohen R, Campos JM, Conte-Devolx B, Maes B, Boneu A, Schlumberger M, Bigorgne JC, Dumontier P, Leclerc L, Corcuff B, Guilhem I. Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Groupe d'étude des tumeurs à calcitonine. Clin Endocrinol (Oxf). 1998. 48:265–273.
17. Dralle H, Scheumann GF, Proye C, Bacourt F, Frilling A, Limbert F, Gheri G, Henry JF, Berner M, Niederle B, et al. The value of lymph node dissection in hereditary medullary thyroid carcinoma: a retrospective, European, multicentre study. J Intern Med. 1995. 238:357–361.
18. Ismailov SI, Piulatova NR. Postoperative calcitonin study in medullary thyroid carcinoma. Endocr Relat Cancer. 2004. 11:357–363.
19. Kim JH, Woo SU, Kim SW, Nam SJ, Seo JM, Yang JH. A clinical study of prognositc factors in medullary thyroid cancer. J Korean Surg Soc. 2004. 66:301–306.
20. Miyauchi A, Onishi T, Morimoto S, Takai S, Matsuzuka F, Kuma K, Maeda M, Kumahara Y. Relation of doubling time of plasma calcitonin levels to prognosis and recurrence of medullary thyroid carcinoma. Ann Surg. 1984. 199:461–466.
21. Barbet J, Campion L, Kraeber-Bodéré F, Chatal JF. GTE Study Group. Prognostic impact of serum calcitonin and carcinoembryonic antigen doubling-times in patients with medullary thyroid carcinoma. J Clin Endocrinol Metab. 2005. 90:6077–6084.
22. Hinze R, Holzhausen HJ, Gimm O, Dralle H, Rath FW. Primary hereditary medullary thyroid carcinoma--C-cell morphology and correlation with preoperative calcitonin levels. Virchows Arch. 1998. 433:203–208.
23. Machens A, Gimm O, Ukkat J, Hinze R, Schneyer U, Dralle H. Improved prediction of calcitonin normalization in medullary thyroid carcinoma patients by quantitative lymph node analysis. Cancer. 2000. 88:1909–1915.
Similar articles