Annals of Surgical Oncology

, Volume 17, Issue 9, pp 2444–2451 | Cite as

Prognostic Value of Histological and Immunohistochemical Characteristics for Predicting the Recurrence of Medullary Thyroid Carcinoma

  • A. Ríos
  • J. M. Rodríguez
  • J. M. Acosta
  • M. D. Balsalobre
  • N. Torregrosa
  • J. Sola
  • D. Pérez-Flores
  • P. Parrilla
Endocrine Tumors



In medullary thyroid carcinoma, there is currently no consensus about the prognostic value of histological and immunohistochemical parameters. This study was designed to analyze the value of various histological and immunohistochemical characteristics for predicting the recurrence of medullary carcinoma.


A total of 55 cases of medullary thyroid carcinoma have been reviewed. These were operated on consecutively between 1971 and 2004 after histological confirmation. The data referring to clinical characteristics and evolution were taken from the patient’s clinical history. The macroscopic, microscopic, and immunohistochemical characteristics of the tumors were taken from the pathological anatomy report.


In 14 (27%) cases, there was recurrence of the disease. The disease-free interval at 1 year was 88 ± 5%; at 5 years 73 ± 7%; at 10 years 73 ± 7%; at 15 years 61 ± 10%; and at 20 years or more 61 ± 10%. Of the histological parameters, only vascular invasion (0.0098) was related to a higher relapse rate. No epidemiological variable or immunohistochemical marker was associated with relapse. However, it was found that staging (P = 0.0102), as well as tumor size (P = 0.0211) and lymph node affectation (P = 0.0012), are factors significantly related to relapse of the disease. According to Cox’s regression model, the only variable with a statistically significant effect was vascular invasion (P = 0.0056; odds ratio = 5.2308).


The overall recurrence rate was 27%, and the main independent prognostic factor of recurrence was tumoral vascular invasion at diagnosis. Staging, tumor size, and lymph node metastasis are prognostic factors of recurrence, although they are not significant in the multivariate analysis.


Calcitonin Vascular Invasion Medullary Thyroid Carcinoma Medullary Carcinoma Immunohistochemical Characteristic 
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  1. 1.
    Weber T, Schilling T, Buchler MW. Thyroid carcinoma. Curr Opin Oncol. 2006;18:30–5.PubMedGoogle Scholar
  2. 2.
    Ríos A, Rodríguez JM, Canteras M, Galindo PJ, Tebar FJ, Parrilla P. Surgical management of multinodular goiter with compression symptoms. Arch Surg. 2005;140:49–53CrossRefPubMedGoogle Scholar
  3. 3.
    Ríos A, Rodríguez JM, Galindo PJ, Canteras M, Parrilla P. Surgical treatment for multinodular goitres in geriatric patients. Langenbeck Arch Surg. 2005;390:236–42CrossRefGoogle Scholar
  4. 4.
    Ríos A, Rodríguez JM, Canteras M, Galindo PJ, Balsalobre MD, Soria T, Parrilla P. Risk factors for malignancy in multinodular goitres. Eur J Surg Oncol. 2004;30:58–62CrossRefPubMedGoogle Scholar
  5. 5.
    Ball DW. Medullary thyroid cancer: monitoring and therapy. Endocrinol Metab Clin North Am. 2007;36:823–37.CrossRefPubMedGoogle Scholar
  6. 6.
    Hoff AD. Medullary thyroid carcinoma. Hematol Oncol Clin North Am. 2007;21:475–88.CrossRefPubMedGoogle Scholar
  7. 7.
    Kebebew E, Ituarte P, Siperstein A, Duh QY, Klark O. Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison OS staging system. Cancer. 2000;88:1139–48.CrossRefPubMedGoogle Scholar
  8. 8.
    Brierley JD, Tsang R, Simpson WJ, Gospodarowicz M, Sutcliffe S, Panzarella T. Medullary thyroid cancer: analyses of survival and prognostic factors and the role of radiation therapy in local control. Thyroid. 1996;6:305–10.CrossRefPubMedGoogle Scholar
  9. 9.
    Franc B, Rosenberg Bourgin M, Caillou B, et al. Medullary thyroid carcinoma: search for histological predictors of survival (109 proband cases analysis). Hum Pathol. 1998;29:1078–84.CrossRefPubMedGoogle Scholar
  10. 10.
    Modigliani E, Cohen R, Campos JM, Conte-Devolx D, Maes B, Boneu A, et al. Prognostic factor for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Clin Endocrinol. 1998;48:265–73.CrossRefGoogle Scholar
  11. 11.
    Gulben K, Berberoglu U, Boyabatli M. Prognostic factors for sporadic medullary thyroid carcinoma. World J Surg. 2006;30:84–90.CrossRefPubMedGoogle Scholar
  12. 12.
    Roman S, Lin R, Sosa JA. Prognosis of medullary thyroid carcinoma: demographic, clinical and pathologic predictors of survival in 1252 cases. Cancer. 2006;107:2134–42.CrossRefPubMedGoogle Scholar
  13. 13.
    Clark JR, Fridman TR, Odell MJ, Brierley J, Walfish PG, Freeman JL. Prognostic variables and calcitonin in medullary thyroid cancer. Laryngoscope. 2005;115(8):1445–50.CrossRefPubMedGoogle Scholar
  14. 14.
    Traugott A, Moley JF. Medullary thyroid cancer: medical management and follow-up. Curr Treat Options Oncol. 2005;6:339–46.CrossRefPubMedGoogle Scholar
  15. 15.
    Helbling B, Wharton K, McLeod MK. Medullary thyroid cancer: the controversy continues. Curr Surg. 2004;61:537–45.CrossRefPubMedGoogle Scholar
  16. 16.
    Albores J, Monforte H, Hadji M, Morales AR. C cell hyperplasia in thyroid tissue adjacent to follicular cell tumors. Hum Pathol. 1988;19:795–9.CrossRefGoogle Scholar
  17. 17.
    Bergholm U, Adami HO, Auer G, Bergstrom R, Backdahl M, et al. Histopathological characteristics and DNA contents as prognostic factor in medullary thyroid carcinoma: a nationwide study in Sweden. Cancer. 1989;64:135–142.CrossRefPubMedGoogle Scholar
  18. 18.
    Hermanek P, Sobin LH, editors. UICC TNM classfication of malignant tumours. 4th ed. Berlin: Springer Verlag; 1987.Google Scholar
  19. 19.
    Dottorini M, Assi A, Sironi M, Sangalli G, Spreafico G, Colombo L. Multivariate analysis of patients with medullary thyroid carcinoma. Prognostic significance and impact on treatment of clinical and pathological variables. Cancer. 1996;77:1556–65.CrossRefPubMedGoogle Scholar
  20. 20.
    Fuchshuber PR, Loree TR, Hicks WL, Cheney RT, Shedd DP. Medullary carcinoma of the thyroid: prognostic factors and treatment recommendations. Ann Surg Oncol. 1998;5:81–6.CrossRefPubMedGoogle Scholar
  21. 21.
    Samaan NA, Schultz PN, Hickey RC. Medullary thyroid carcinoma. Prognosis of familial versus sporadic disease and the role of radiotherapy. J Clin Endocrinol Metab. 1988;7:801–5.CrossRefGoogle Scholar
  22. 22.
    Ukkat J, Gimm O, Brauckhoff M, Bilkenroth U, Dralle H. Single center experience in primary surgery for medullary thyroid carcinoma. World J Surg. 2004;28:1271–4.CrossRefPubMedGoogle Scholar
  23. 23.
    Brauckhoff M, Lorenz K, Ukkat J, Brauckhoff K, Gimm O, Dralle H. Medullary thyroid carcinoma. Scand J Surg. 2004;93:249–60.PubMedGoogle Scholar
  24. 24.
    Gimm O, Ukkat J, Niederle BE, Weber T, Thanh PN, Brauckhoff M, Niederle B, Dralle H. Timing and extent of surgery in patients with familial medullary thyroid carcinoma/multiple endocrine neoplasia 2A-related RET mutations not affecting codon 634. World J Surg. 2004;28:1312–6.CrossRefPubMedGoogle Scholar
  25. 25.
    Hyer SL, Vini L, A’Hern R, Harmer C. Medullary thyroid cancer: multivariate analyses of prognostic factors influencing survival. Eur J Surg Oncol. 2000;26:686–90.CrossRefPubMedGoogle Scholar
  26. 26.
    Kakudo K, Carney JA, Sizemore GW. Medullary carcinoma of the thyroid. Biological behavior of the sporadic and familial neoplasm. Cancer. 1985;55:2818–21.CrossRefPubMedGoogle Scholar
  27. 27.
    Saad MF, Ordonez NG, Rashid RK, Guido JJ, Hill CS Jr, Hickey RC, Samaan NA. Medullary carcinoma of the thyroid. A study of the clinical features and prognostic factors in 161 patients. Medicine (Baltimore). 1984;63:319–42.Google Scholar
  28. 28.
    Schröder S, Böcker W, Baisch H, et al. Prognostic factor in medullary thyroid carcinoma. Survival in relation to age, sex, stage, histology, immunocytochemistry and DNA content. Cancer. 1988;61:806–16.CrossRefPubMedGoogle Scholar
  29. 29.
    Williams ED, Brown CL, Doniach I. Pathological and clinical findings in a series of 67 medullary carcinoma of the thyroid. J Clin Pathol. 1966;19:103–13.CrossRefPubMedGoogle Scholar
  30. 30.
    Holm R, Sobrinho M, Nesland JM, Gould VE, Johanness JV. Medullary carcinoma of the thyroid gland: an immunocytochemical study. Ultrastruct Pathol. 1985;8:25–41.CrossRefPubMedGoogle Scholar
  31. 31.
    Pyke CM, Hay ID, Goellner JR, Bergstrahl EJ, van Heerden JA, Grant CS. Prognostic significance of calcitonin immunoreactivity, amyloid staining, and flow cytometric DNA measurements in medullary thyroid carcinoma. Surgery. 1991;110:964–70.PubMedGoogle Scholar
  32. 32.
    Bergholm U, Bergstrom R, Ekbom A. Long-term follow-up of patients with medullary carcinoma of the thyroid. Cancer. 1997;79:132–8.CrossRefPubMedGoogle Scholar
  33. 33.
    Fontanini G, Vignati S, Pacini F, Pollina L, Basolo F. Microvessel count: an indicator of poor outcome in medullary thyroid carcinoma but not in other types of thyroid carcinoma. Mod Pathol. 1996;9:634–41.Google Scholar
  34. 34.
    Bigner SH, Cox EB, Mendelsohn G, Baylin SB, Wells SA Jr, Eggleston JC. Medullary carcinoma of the thyroid in the multiple endocrine neoplasia 2A syndrome. Am J Surg Pathol. 1981;5:459–72.CrossRefPubMedGoogle Scholar
  35. 35.
    Saad MF, Ordonez NG, Guido JJ, Samaan NA. The prognostic value of calcitonin immunostaining in medullary carcinoma of the thyroid. J Clin Endocrinol Metab. 1984;59:850–6.CrossRefPubMedGoogle Scholar
  36. 36.
    Pacini F, Basolo F, Rossella E, Fugazzola L, Cola A, Pinchera A. Medullary thyroid cancer: an immunohistochemical and humoral study using six separate antigens. Am J Clin Pathol. 1991;95:300–8.PubMedGoogle Scholar
  37. 37.
    Pollina L, Pacini F, Fontanini G, Vignati S, Bevilacqua G, Basolo F. Bcl-2, p53 and proliferating cell nuclear antigen expression is related to the degree of differentiation in thyroid carcinomas. Br J Cancer. 1996;73:139–43.PubMedGoogle Scholar
  38. 38.
    Wang DG, Liu WH, Johnston CF, Sloan JM, Buchanan KD. Bcl-2 and c-Myc, but not bax and p53, are expressed during human medullary thyroid tumorogenesis. Am J Pathol. 1998;152:1407–13.PubMedGoogle Scholar
  39. 39.
    Viale G, Roncalli M, Grimelius L, et al. Prognostic value of bcl-2 immunoreactivity in medullary thyroid carcinoma. Hum Pathol. 1995;26:945–50.CrossRefPubMedGoogle Scholar
  40. 40.
    Goldenberg JD, Portugal LG, Wenig BL, Ferrer K, Wu JC, Sabnani J. Well-differentiated thyroid carcinoma: p53 status and microvessel density. Head Neck. 1998;20:152–8.CrossRefPubMedGoogle Scholar
  41. 41.
    Horii A, Yoshida J, Sakai M, Okamoto S, et al. Ki-67 positive fractions in benign and malignant thyroid tumours: application of flow cytometry. Acta Otolaryngol. 1999;119:617–20CrossRefPubMedGoogle Scholar
  42. 42.
    Tisell LE, Oden A, Muth A, Altiparmak G, Molne J, Ahlman H, Nilsson O. The Ki67 index a prognostic marker in medullary thyroid carcinoma. Br J Cancer. 2003;89:2093–7.CrossRefPubMedGoogle Scholar
  43. 43.
    Yokota J, Yamamoto T, Toyoshima K, et al. Amplification of the c-erb-B2 oncogene in human adenocarcinomas in vivo. Lancet. 1986;1:765–7.CrossRefPubMedGoogle Scholar
  44. 44.
    Soda G, Antonaci A, Bosco D, Nardoni S, Melis M. Expression of bcl-2, c-erb-B2, p53, and p21 (wafl-cip1) protein in thyroid carcinoma. J Exp Clin Cancer Res. 1999;18:363–70.PubMedGoogle Scholar
  45. 45.
    Ito Y, Yoshida H, Motoo Y, Iovanna JL, Tomoda C, Uruno T, Takamura Y, Miya A, Kobayashi K, Matsuzuka F, Kuma K, Miyauchi A. Expression of p8 protein in medullary thyroid carcinoma. Anticancer Res. 2005;25:3419–23.PubMedGoogle Scholar
  46. 46.
    Ito Y, Yoshida H, Tomoda C, Uruno T, Takamura Y, Miya A, Kobayashi K, Matsuzuka F, Kuma K, Nakamura Y, Kakudo K, Miyauchi A. Expression of cdc25B and cdc25A in medullary thyroid carcinoma: cdc25B expression level predicts a poor prognosis. Cancer Lett. 2005;229:291–7.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2010

Authors and Affiliations

  • A. Ríos
    • 1
    • 4
  • J. M. Rodríguez
    • 1
  • J. M. Acosta
    • 2
  • M. D. Balsalobre
    • 1
  • N. Torregrosa
    • 1
  • J. Sola
    • 2
  • D. Pérez-Flores
    • 3
  • P. Parrilla
    • 1
  1. 1.Servicio de Cirugía General y del Aparato Digestivo IHospital Universitario Virgen de la ArrixacaEl PalmarSpain
  2. 2.Servicio de Anatomía PatológicaHospital Universitario Virgen de la ArrixacaEl PalmarSpain
  3. 3.Departamento de Bioestadística de la Universidad de MurciaHospital Universitario Virgen de la ArrixacaEl PalmarSpain
  4. 4.Avenida de la Libertad no 208CasillasSpain

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