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

Ann Surg Oncol. 2016 Sep;23(9):2883-8. doi: 10.1245/s10434-016-5245-9. Epub 2016 May 4.

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.

MeSH terms

  • Adult
  • Carcinoma, Papillary / genetics
  • Carcinoma, Papillary / metabolism*
  • Carcinoma, Papillary / secondary*
  • Cell Adhesion Molecules / metabolism*
  • Female
  • Humans
  • Lymphatic Metastasis
  • Male
  • Membrane Proteins
  • Middle Aged
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins B-raf / genetics
  • RNA-Binding Proteins
  • Thyroid Gland / metabolism
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism*
  • Thyroid Neoplasms / pathology*

Substances

  • Cell Adhesion Molecules
  • MTDH protein, human
  • Membrane Proteins
  • RNA-Binding Proteins
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf