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Virchows Archiv

, Volume 472, Issue 3, pp 461–468 | Cite as

Large sporadic thyroid medullary carcinomas: predictive factors for lymph node involvement

  • Sébastien Aubert
  • Amandine Berdelou
  • Viviane Gnemmi
  • Hélène Behal
  • Robert Caiazzo
  • Michèle D’herbomez
  • Pascal Pigny
  • Jean Louis Wemeau
  • Bruno Carnaille
  • Florence Renaud
  • Brigitte Bouchindhomme
  • Emmanuelle Leteurtre
  • Michael Perrais
  • François Pattou
  • Christine Do Cao
Original Article

Abstract

Lymph node involvement (LNI) is one of the most important prognostic factors for poor survival in medullary thyroid carcinoma (MTC). At diagnosis, LNI is found in over 50% of sporadic MTCs, and especially in large tumours. Cervical lymph node dissection is therefore mandatory during MTC surgery. However, some large tumours (responsible for high preoperative basal calcitonin levels) are found to lack LNI, and can be cured definitely. Preoperative detection of these particular tumours might spare patients from undergoing extensive cervical dissection. The objective of the present retrospective study of a series of large sporadic MTCs was to identify clinical, biological and pathological factors that were predictive of LNI. Consecutive cases of large, sporadic MTCs (measuring at least 1 cm in diameter) were retrieved and reviewed. The levels of several mature microRNAs (miRs) in paraffin-embedded samples were assessed using qPCR. Of the 54 MTCs, 26 had LNI and 28 were pN0. Relative to pN0 patients, patients with LNI had a significant higher preoperative basal calcitonin level (p = 0.0074) and a greater prevalence of infiltrative margins (p < 0.0001), lymphovascular invasion (p = 0.0004), extrathyroidal extension (p < 0.0001), a higher pT stage (p = 0.0003) and more abundant desmoplastic stroma (p = 0.0006). Tumour expression levels of miR-21 (p = 0.0008) and miR-183 (p = 0.0096) were higher in the LNI group. The abundance of desmoplastic stroma (p = 0.007) and the miR-21 expression level (p = 0.0026) were independent prognostic factors for LNI. The abundance of desmoplastic stroma and high levels of miR-21 expression were strong indicators of LNI, and may thus help the surgeon to choose the extent of cervical lymph node dissection for large, sporadic MTCs with no preoperatively obvious LNI.

Keywords

Medullary Thyroid Carcinoma Node Desmoplasia MicroRNA 

Notes

Acknowledgements

We thank B Hémon (UMR 1172, Lille) for excellent technical assistance.

Author contribution

All authors made substantial contributions to the conception and design of the work; acquisition, analysis and interpretation of data; and drafting and revising of the manuscript for important intellectual content. They approved the final version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Compliance with ethical standards

The present study was approved by the scientific advisory board at our institution’s biobank (Tumorothèque du C2RC, Lille, France, reference: CSTMT106).

Conflict of interest

The authors declare that they have no conflicts of interest.

Informed consent

All patients having undergone a RET gene mutation analysis on a sample of lymphocyte DNA had given their written, informed consent.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Sébastien Aubert
    • 1
    • 2
    • 3
  • Amandine Berdelou
    • 4
  • Viviane Gnemmi
    • 1
    • 2
    • 3
  • Hélène Behal
    • 5
  • Robert Caiazzo
    • 2
    • 6
  • Michèle D’herbomez
    • 7
  • Pascal Pigny
    • 2
    • 3
    • 7
  • Jean Louis Wemeau
    • 2
    • 8
  • Bruno Carnaille
    • 2
    • 6
  • Florence Renaud
    • 1
    • 2
    • 3
  • Brigitte Bouchindhomme
    • 1
  • Emmanuelle Leteurtre
    • 1
    • 2
    • 3
  • Michael Perrais
    • 2
    • 3
  • François Pattou
    • 2
    • 6
  • Christine Do Cao
    • 8
  1. 1.Institut de Pathologie, Centre de Biologie PathologieCHRU de LilleLilleFrance
  2. 2.Faculté de MédecineUniversité de LilleLilleFrance
  3. 3.UMR 1172INSERM Bâtiment Biserte, JPArcLilleFrance
  4. 4.Service de Cancérologie endocrinienneIGRParisFrance
  5. 5.Unité de Biostatistiques - Pôle de Santé PubliqueCHRU de LilleLilleFrance
  6. 6.Service de Chirurgie Endocrine, Hôpital HuriezCHRU de LilleLilleFrance
  7. 7.Institut de Biochimie, Centre de Biologie Pathologie GénétiqueCHRU de LilleLilleFrance
  8. 8.Service d’Endocrinologie, Hôpital HuriezCHRU de LilleLilleFrance

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