A comparative study of nuclear 8-hydroxyguanosine expression in Autoimmune Thyroid Diseases and Papillary Thyroid Carcinoma and its relationship with p53, Bcl-2 and Ki-67 cancer related proteins

Adv Med Sci. 2017 Mar;62(1):45-51. doi: 10.1016/j.advms.2016.06.003. Epub 2016 Jun 22.

Abstract

Purpose: To investigate whether the oxidative stress is involved in the evolution of Graves' disease (GD) and Hashimoto thyroiditis (HT) into Papillary Thyroid Carcinoma (PTC), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and cancer related proteins (Bcl-2, p53 and Ki-67) expressions were evaluated in these pathologies.

Patients and methods: Immunohistochemical method was applied on 25 thyroid tissues. Allred score (AS) serving to evaluate the immunostaining is based on a scale from 0 to 8. "Negligible expression" was assigned to a score of 0 to 2, "expression" and "overexpression" were attributed to a score of 3-5 and ≥6 respectively.

Results: PTC cancer cells exhibited 100% 8-OHdG "overexpression" compared to 87.5% in PTC non-malignant epithelial (NME) ones (p<0.05). Higher 8-OHdG AS was found in PTC NME cells compared to GD and HT (p<0.001, p<0.05 respectively). "Overexpression" of Bcl-2 was noted in all PTC cell types. Remarkably, just like the PTC cancer and NME cells 33.3% of HT and 50% of GD patients' revealed simultaneous "overexpression" of Bcl-2 and 8-OHdG in epithelial cells. No staining was detected for p53 in all pathologies. PTC lymphoid cells exhibited 100% "overexpression" for 8-OHdG and Bcl-2 with concomitant "negligible expression" for Ki-67 in 87.5% of patients. In contrast, HT lymphoid cells showed 22.2% "expression" and GD 62.5% "expression" and 12.5% "overexpression" of Ki-67.

Conclusions: Simultaneous "overexpression" of 8-OHdG and Bcl-2 in GD and HT could be considered as prognostic markers while "negligible expression" of Ki-67 in PTC lymphoid cells suggests an anergic state favoring the tumor escapes from the immune system.

Keywords: 8-OHdG; Graves's disease; Hashimoto thyroiditis; Papillary Thyroid Carcinoma.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Papillary / diagnosis*
  • Carcinoma, Papillary / etiology
  • Carcinoma, Papillary / metabolism
  • Cell Nucleus / metabolism*
  • Female
  • Follow-Up Studies
  • Graves Disease / complications*
  • Guanosine / analogs & derivatives*
  • Guanosine / metabolism
  • Hashimoto Disease / complications*
  • Humans
  • Ki-67 Antigen / metabolism*
  • Male
  • Oxidative Stress
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / diagnosis*
  • Thyroid Neoplasms / etiology
  • Thyroid Neoplasms / metabolism
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Guanosine
  • 8-hydroxyguanosine