title: Midkine concentrations in fine-needle aspiration of benign and malignant thyroid nodules.
abstract: BACKGROUND
  The primary preoperative method for distinguishing malignant from benign thyroid nodules is fine-needle aspiration (FNA) cytology, but it is frequently inconclusive. Midkine (MDK) is a heparin-binding growth factor, which is overexpressed in papillary thyroid carcinoma (PTC).
  
  
  OBJECTIVE
  We measured MDK concentrations in FNA samples from benign and malignant thyroid nodules to explore the possibility that MDK measurement might aid in the evaluation of thyroid nodules.
  
  
  METHODS
  35 subjects underwent preoperative FNA of 45 thyroid nodules, followed by thyroidectomy, providing a histological diagnosis. FNA needle contents were first expressed for cytology, and then, the needle was washed with buffer for immunoassay. In 46 subjects without preoperative FNA samples, FNA was performed ex vivo on 62 nodules within surgically excised thyroid tissue.
  
  
  METHODS
  MDK was measured using a high-sensitivity sandwich ELISA and normalized to thyroglobulin (Tg) concentration in the sample to adjust for tissue content in the aspirate.
  
  
  RESULTS
  The MDK/Tg ratio was higher in 18 PTCs than in 87 benign nodules (204 ± 106 vs 1·2 ± 0·3 ng/mg, mean ± SEM, P < 0·001). Using a threshold of 10 ng/mg, the sensitivity and specificity of the MDK/Tg ratio for diagnosis of PTC were 67% and 99%, respectively. All follicular variant PTCs had a MDK/Tg ratio <10 ng/mg.
  
  
  CONCLUSIONS
  The findings indicate that, in FNA samples, the MDK/Tg ratio in PTC is greater than in benign thyroid nodules, raising the possibility that this approach might provide adjunctive diagnostic or prognostic information to complement existing approaches.
authors.affiliation: Section on Growth and Development, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Youn Hee
authors.initials: YH
authors.lastname: Jee
authors.affiliation: Division of Endocrinology and Metabolism, Virginia Commonwealth University, Bethesda, MD, USA.
authors.forename: Francesco S
authors.initials: FS
authors.lastname: Celi
authors.affiliation: Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Maureen
authors.initials: M
authors.lastname: Sampson
authors.affiliation: Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Sacks
authors.affiliation: Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Alan T
authors.initials: AT
authors.lastname: Remaley
authors.affiliation: Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Electron
authors.initials: E
authors.lastname: Kebebew
authors.affiliation: Section on Growth and Development, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Baron
mesh_terms: D044963:Biopsy, Fine-Needle / Q000379:methods*; D016207:Cytokines / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000078792:Midkine; D013954:Thyroglobulin / Q000032:analysis*; D016606:Thyroid Nodule / Q000737:chemistry*
chemical_list: D016207:Cytokines; D000078792:Midkine; D013954:Thyroglobulin