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Metadherin Expression is Associated with Extrathyroidal Extension in Papillary Thyroid Cancer Patients

  • Endocrine Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Metadherin (MTDH) is widely recognized as a promising molecular marker for tumor recurrence and poor survival in many cancers. By multiple pathways, MTDH promotes oncogenesis, metastasis, and chemoresistance. This study investigated the role of MTDH in papillary thyroid carcinoma (PTC) to determine its potential association with aggressive clinical and pathologic features, including its relation in tumors harboring a BRAF V600E mutation.

Methods

Expression of MTDH was assessed by immunohistochemistry in 96 cases of PTC, including primary thyroid malignancies and lymph node metastases. The status of BRAF V600E mutation was determined by real-time polymerase chain reaction.

Results

Overexpression of MTDH was observed in 26 % (23/88) of primary PTC cases. High-intensity staining was observed in 75 % (6/8) of lymph nodes with metastatic PTC and moderate staining in 25 % (2/8) of cases. Normal adjacent thyroid tissue and benign thyroid controls were found to have significantly lower MTDH expression than cancer tissue (p < 0.05). Apical staining of MTDH was observed in 19 % of thyroid tumors and not observed in normal thyroid tissue. Interestingly, MTDH expression was associated with extrathyroidal extension (p < 0.05) and not associated with age, gender, overall tumor stage, or BRAF V600E mutation status.

Conclusion

In a subset of PTC patients, MTDH was overexpressed and associated with extrathyroidal extension. Further studies are warranted to explore the utility of MTDH to improve risk stratification of current molecular panels for PTC.

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References

  1. Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA. 2006;295:2164–7.

    Article  CAS  PubMed  Google Scholar 

  2. Howlader N, Noone A, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975–2012. National Cancer Institute, 2015. http://seer.cancer.gov/csr/1975_2012/

  3. Schlumberger MJ. Papillary and follicular thyroid carcinoma. N Engl J Med. 1998;338:297–306.

    Article  CAS  PubMed  Google Scholar 

  4. Yarchoan M, LiVolsi VA, Brose MS. BRAF mutation and thyroid cancer recurrence. J Clin Oncol. 2015;33:7–8.

    Article  PubMed  Google Scholar 

  5. Howell GM, Nikiforova MN, Carty SE, et al. BRAF V600E mutation independently predicts central compartment lymph node metastasis in patients with papillary thyroid cancer. Ann Surg Oncol. 2013;20:47–52.

    Article  PubMed  Google Scholar 

  6. Li X, Abdel-Mageed AB, Kandil E. BRAF mutation in papillary thyroid carcinoma. Int J Clin Exp Med. 2012;5:310–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Xing M. Prognostic utility of BRAF mutation in papillary thyroid cancer. Mol Cell Endocrinol. 2010;321:86–93.

    Article  CAS  PubMed  Google Scholar 

  8. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417:949–54.

    Article  CAS  PubMed  Google Scholar 

  9. Xing M, Alzahrani AS, Carson KA, et al. Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA. 2013;309:1493–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. George JR, Henderson YC, Williams MD, et al. Association of TERT promoter mutation, but not BRAF mutation, with increased mortality in PTC. J Clin Endocrinol Metab. 2015;100:E1550–9.

    Article  PubMed  Google Scholar 

  11. Fugazzola L, Puxeddu E, Avenia N, et al. Correlation between B-RAFV600E mutation and clinicopathologic parameters in papillary thyroid carcinoma: data from a multicentric Italian study and review of the literature. Endocr Relat Cancer. 2006;13:455–64.

    Article  CAS  PubMed  Google Scholar 

  12. Xing M, Alzahrani AS, Carson KA, et al. Association between BRAF V600E mutation and recurrence of papillary thyroid cancer. J Clin Oncol. 2015;33:42–50.

    Article  PubMed  Google Scholar 

  13. Henke LE, Pfeifer JD, Ma C, et al. BRAF mutation is not predictive of long-term outcome in papillary thyroid carcinoma. Cancer Med. 2015;4:791–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Li C, Lee KC, Schneider EB, Zeiger MA. BRAF V600E mutation and its association with clinicopathological features of papillary thyroid cancer: a meta-analysis. J Clin Endocrinol Metab. 2012;97:4559–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kim TH, Park YJ, Lim JA, et al. The association of the BRAF(V600E) mutation with prognostic factors and poor clinical outcome in papillary thyroid cancer: a meta-analysis. Cancer. 2012;118:1764–73.

    Article  CAS  PubMed  Google Scholar 

  16. Lee JH, Lee ES, Kim YS. Clinicopathologic significance of BRAF V600E mutation in papillary carcinomas of the thyroid: a meta-analysis. Cancer. 2007;110:38–46.

    Article  PubMed  Google Scholar 

  17. Wang Z, Chen JQ, Liu JL, Qin XG. Clinical impact of BRAF mutation in the diagnosis and prognosis of papillary thyroid carcinoma: a systematic review and meta-analysis. Eur J Clin Invest. 2015;46:146–57.

    Article  Google Scholar 

  18. Huang Y, Li LP. Progress of cancer research on astrocyte elevated gene-1/Metadherin (review). Oncol Lett. 2014;8:493–501.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Li WF, Wang G, Zhao ZB, Liu CA. High expression of metadherin correlates with malignant pathological features and poor prognostic significance in papillary thyroid carcinoma. Clin Endocrinol Oxford. 2015;83:572–80.

    Article  CAS  Google Scholar 

  20. Hu G, Wei Y, Kang Y. The multifaceted role of MTDH/AEG-1 in cancer progression. Clin Cancer Res. 2009;15:5615–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Li WF, Dai H, Ou Q, Zuo GQ, Liu CA. Overexpression of microRNA-30a-5p inhibits liver cancer cell proliferation and induces apoptosis by targeting MTDH/PTEN/AKT pathway. Tumour Biol. 2015. doi:10.1007/s13277-015-4456-1.

    Google Scholar 

  22. Liu P, Tang H, Chen B, et al. miR-26a suppresses tumour proliferation and metastasis by targeting metadherin in triple negative breast cancer. Cancer Lett. 2015;357:384–92.

    Article  CAS  PubMed  Google Scholar 

  23. Wang Z, Wang L, Hu J, Fan R, Zhou J, Zhong J. RARRES3 suppressed metastasis through suppression of MTDH to regulate epithelial-mesenchymal transition in colorectal cancer. Am J Cancer Res. 2015;5:1988–99.

    PubMed  PubMed Central  Google Scholar 

  24. Zhu GC, Yu CY, She L, et al. Metadherin regulation of vascular endothelial growth factor expression is dependent upon the PI3K/Akt pathway in squamous cell carcinoma of the head and neck. Medicine. 2015;94:e502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Liu Y, Kong X, Li X, Li B, Yang Q. Knockdown of metadherin inhibits angiogenesis in breast cancer. Int J Oncol. 2015;46:2459–66.

    PubMed  Google Scholar 

  26. Liang Y, Hu J, Li J, et al. Epigenetic activation of TWIST1 by MTDH promotes cancer stem-like cell traits in breast cancer. Cancer Res. 2015;75:3672–80.

    Article  CAS  PubMed  Google Scholar 

  27. Song Z, Wang Y, Li C, Zhang D, Wang X. Molecular modification of metadherin/MTDH impacts the sensitivity of breast cancer to doxorubicin. PLoS ONE. 2015;10:e0127599.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Wei YB, Guo Q, Gao YL, et al. Repression of metadherin inhibits biological behavior of prostate cancer cells and enhances their sensitivity to cisplatin. Mol Med Rep. 2015;12:226–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Jung HI, Ahn T, Bae SH, et al. Astrocyte elevated gene-1 overexpression in hepatocellular carcinoma: an independent prognostic factor. Ann Surg Treat Res. 2015;88:77–85.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Zhou B, Yang J, Shu B, et al. Overexpression of astrocyte-elevated gene-1 is associated with ovarian cancer development and progression. Mol Med Rep. 2015;11:2981–90.

    CAS  PubMed  Google Scholar 

  31. Huang K, Li LA, Meng Y, You Y, Fu X, Song L. High expression of astrocyte elevated gene-1 (AEG-1) is associated with progression of cervical intraepithelial neoplasia and unfavorable prognosis in cervical cancer. World J Surg Oncol. 2013;11:297.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Gnosa S, Shen YM, Wang CJ, et al. Expression of AEG-1 mRNA and protein in colorectal cancer patients and colon cancer cell lines. J Transl Med. 2012;10:109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Casimiro S, Fernandes A, Oliveira AG, et al. Metadherin expression and lung relapse in patients with colorectal carcinoma. Clin Exp Metastasis. 2014;31:689–96.

    Article  CAS  PubMed  Google Scholar 

  34. Zhang C, Li HZ, Qian BJ, Liu CM, Guo F, Lin MC. MTDH/AEG-1-based DNA vaccine suppresses metastasis and enhances chemosensitivity to paclitaxel in pelvic lymph node metastasis. Biomed Pharmacother. 2015;70:217–26.

    Article  CAS  PubMed  Google Scholar 

  35. Qian BJ, Yan F, Li N, et al. MTDH/AEG-1-based DNA vaccine suppresses lung metastasis and enhances chemosensitivity to doxorubicin in breast cancer. Cancer Immunol Immunother. 2011;60:883–93.

    Article  CAS  PubMed  Google Scholar 

  36. Tang J, Shen L, Yang Q, Zhang C. Overexpression of metadherin mediates metastasis of osteosarcoma by regulating epithelial-mesenchymal transition. Cell Prolif. 2014;47:427–34.

    Article  CAS  PubMed  Google Scholar 

  37. Adeniran AJ, Theoharis C, Hui P, et al. Reflex BRAF testing in thyroid fine-needle aspiration biopsy with equivocal and positive interpretation: a prospective study. Thyroid. 2011;21:717–23.

    Article  CAS  PubMed  Google Scholar 

  38. Nikiforov YE, Carty SE, Chiosea SI, et al. Impact of the multi-gene ThyroSeq next-generation sequencing assay on cancer diagnosis in thyroid nodules with atypia of undetermined significance/follicular lesion of undetermined significance cytology. Thyroid. 2015;25:1217–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Xing M, Liu R, Liu X, et al. BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence. J Clin Oncol. 2014;32:2718–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Conflict of interest

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Authors and Affiliations

  1. Oncological Surgery Division, Department of Surgery, Tulane University School of Medicine, New Orleans, LA, USA

    Robert F. Moore BA, Zaid Al-Qurayshi MD, Koji Tsumagari MD, PhD, Obinwanne M. Emejulu MD, Roostam Kholmatov MD, Zakaria Y. Abd Elmageed MD & Emad Kandil MD, MBA, FACS, FACE

  2. Department of Pathology, Tulane University School of Medicine, New Orleans, LA, USA

    Andrew B. Sholl MD & Laura Kidd MD

  3. Department of Otolaryngology, Tulane University School of Medicine, New Orleans, LA, USA

    Paul Friedlander MD

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  1. Robert F. Moore BA
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  2. Andrew B. Sholl MD
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  4. Zaid Al-Qurayshi MD
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  5. Koji Tsumagari MD, PhD
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  9. Zakaria Y. Abd Elmageed MD
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  10. Emad Kandil MD, MBA, FACS, FACE
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Correspondence to Emad Kandil MD, MBA, FACS, FACE.

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Moore, R.F., Sholl, A.B., Kidd, L. et al. Metadherin Expression is Associated with Extrathyroidal Extension in Papillary Thyroid Cancer Patients. Ann Surg Oncol 23, 2883–2888 (2016). https://doi.org/10.1245/s10434-016-5245-9

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  • DOI: https://doi.org/10.1245/s10434-016-5245-9

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