Increased Pleiotrophin Concentrations in Papillary Thyroid Cancer

PLoS One. 2016 Feb 25;11(2):e0149383. doi: 10.1371/journal.pone.0149383. eCollection 2016.

Abstract

Background: Thyroid nodules are common, and approximately 5% of these nodules are malignant. Pleiotrophin (PTN) is a heparin-binding growth factor which is overexpressed in many cancers. The expression of PTN in papillary thyroid cancer (PTC) is unknown.

Method and findings: 74 subjects (age 47 ± 12 y, 15 males) who had thyroidectomy with a histological diagnosis: 79 benign nodules and 23 PTCs (10 classic, 6 tall cell, 6 follicular variant and 1 undetermined). Fine-needle aspiration (FNA) samples were obtained ex vivo from surgically excised tissue and assayed for PTN and thyroglobulin (Tg). Immunohistochemistry (IHC) was performed on tissue sections. In FNA samples, PTN concentration normalized to Tg was significantly higher in PTC than in benign nodules (16 ± 6 vs 0.3 ± 0.1 ng/mg, p < 0.001). In follicular variant of PTC (n = 6), the PTN/Tg ratio was also higher than in benign nodules (1.3 ± 0.6 vs 0.3 ± 0.1 ng/mg, P < 0.001, respectively). IHC showed cytoplasmic localization of PTN in PTC cells.

Conclusion: In ex vivo FNA samples, the PTN to thyroglobulin ratio was higher in PTCs, including follicular variant PTC, than in benign thyroid nodules. The findings raise the possibility that measurement of the PTN to Tg ratio may provide useful diagnostic and/or prognostic information in the evaluation of thyroid nodules.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Biopsy, Fine-Needle
  • Carcinoma / diagnosis
  • Carcinoma / genetics
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Carcinoma, Papillary
  • Carrier Proteins / metabolism*
  • Cytokines / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Midkine
  • Mutation
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics
  • Thyroglobulin / metabolism
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / diagnosis
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism*
  • Thyroid Neoplasms / pathology

Substances

  • Carrier Proteins
  • Cytokines
  • pleiotrophin
  • Midkine
  • Thyroglobulin
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf