Immunohistochemical evaluation of midkine and nuclear factor-kappa B as diagnostic biomarkers for papillary thyroid cancer and synchronous metastasis

Life Sci. 2014 Nov 18;118(1):39-45. doi: 10.1016/j.lfs.2014.09.025. Epub 2014 Oct 2.

Abstract

Aims: Midkine (MK) is a multifunctional cytokine identified to be a promising cancer biomarker. Nuclear factor-kappa B (NF-κB) is an important transcription factor that plays a pivotal role in tumorigenesis. We aimed to investigate values of MK and NF-κB as markers for diagnosis and synchronous metastasis prediction in papillary thyroid cancer (PTC).

Main methods: 76 cases of PTC and 70 cases of multi-nodular goiter (MNG) were retrieved. The PTC group was further divided into subgroup 1 (16 cases with synchronous metastases) and subgroup 2 (60 cases without metastases). A retrospective review of demographic and clinical information was performed. Immunohistochemistry of MK, NF-κB p65 and Ki-67 was performed on paraffin-embedded specimens and results were quantified. Diagnostic values of the parameters were conducted by receiver operating characteristic (ROC) curves. Protein levels of MK and NF-κB p65 were then confirmed by Western blot.

Key findings: Immunoreactivities of MK, NF-κB p65 and Ki-67 were significantly higher in the PTC group than in the MNG group with good differential diagnostic capabilities. Moreover, immunoreactivities of all three parameters were significantly higher in subgroup 1 than in subgroup 2 with good synchronous metastasis predictive efficacies. Western blot showed that MK and NF-κB p65 protein levels in lesions from subgroup 1 were significantly higher than those from subgroup 2, both of which were significantly higher than in MNG lesions.

Significance: We discovered that MK and NF-κB immunohistochemistries can potentially be used for differential diagnosis between PTC and MNG, and for prediction of synchronous metastases.

Keywords: Midkine (MK); Multi-nodular goiter (MNG); Nuclear factor-kappa B (NF-κB); Papillary thyroid cancer (PTC); Receiver operating characteristic (ROC) curves; Synchronous metastasis.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / metabolism
  • Carcinoma / metabolism*
  • Carcinoma / pathology*
  • Carcinoma, Papillary
  • Female
  • Goiter, Nodular / metabolism
  • Humans
  • Immunohistochemistry / methods
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Midkine
  • Nerve Growth Factors / analysis
  • Nerve Growth Factors / metabolism*
  • Predictive Value of Tests
  • Retrospective Studies
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / metabolism*
  • Thyroid Neoplasms / pathology*
  • Transcription Factor RelA / analysis
  • Transcription Factor RelA / metabolism*

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • MDK protein, human
  • Nerve Growth Factors
  • RELA protein, human
  • Transcription Factor RelA
  • Midkine

Supplementary concepts

  • Goiter, Multinodular 2