title: Immunohistochemical evaluation of midkine and nuclear factor-kappa B as diagnostic biomarkers for papillary thyroid cancer and synchronous metastasis.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, Tianjin Medical University General Hospital, Tianjin, PR China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China. Electronic address: jamesmencius@163.com.
authors.forename: Zhaowei
authors.initials: Z
authors.lastname: Meng
authors.affiliation: Department of Pathology, Tianjin First Center Hospital, Tianjin, PR China.
authors.forename: Mingfang
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China. Electronic address: tanposta@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Tan
authors.affiliation: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, PR China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Tian
authors.affiliation: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, PR China.
authors.forename: Xianghui
authors.initials: X
authors.lastname: He
authors.affiliation: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Endocrinology, Tianjin Medical University General Hospital, Tianjin, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Endocrinology, Tianjin Medical University General Hospital, Tianjin, PR China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China.
authors.forename: Guizhi
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China.
authors.forename: Yajing
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Jia
authors.affiliation: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China; Department of Nuclear Medicine, Second Affiliated Hospital of Zhejiang Medical University, Hangzhou, PR China.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Song
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology*; D002291:Carcinoma, Papillary; D005260:Female; D006044:Goiter, Nodular / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000078792:Midkine; D009414:Nerve Growth Factors / Q000032:analysis / Q000378:metabolism*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051996:Transcription Factor RelA / Q000032:analysis / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; C066254:MDK protein, human; D009414:Nerve Growth Factors; C498143:RELA protein, human; D051996:Transcription Factor RelA; D000078792:Midkine
keywords: Midkine (MK); Multi-nodular goiter (MNG); Nuclear factor-kappa B (NF-κB); Papillary thyroid cancer (PTC); Receiver operating characteristic (ROC) curves; Synchronous metastasis