title: 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.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Laboratory of Analysis, Development and Food Safety, Research Group "Biotechnology and Pathology", National School of Engineers of Sfax, Sfax, Tunisia. Electronic address: malek.mseddi@gmail.com.
authors.forename: Malek
authors.initials: M
authors.lastname: Mseddi
authors.affiliation: Laboratory of Analysis, Development and Food Safety, Research Group "Biotechnology and Pathology", National School of Engineers of Sfax, Sfax, Tunisia.
authors.forename: Riadh
authors.initials: R
authors.lastname: Ben Mansour
authors.affiliation: Department of Anatomy and Pathological Cytology, Habib Bourguiba University Hospital, Sfax, Tunisia.
authors.forename: Naourez
authors.initials: N
authors.lastname: Gouiia
authors.affiliation: Department of Endocrinology Internal and External, Hedi Chaker University Hospital, Sfax, Tunisia.
authors.forename: Fatma
authors.initials: F
authors.lastname: Mnif
authors.affiliation: Laboratory of Analysis, Development and Food Safety, Research Group "Biotechnology and Pathology", National School of Engineers of Sfax, Sfax, Tunisia.
authors.forename: Rabï
authors.initials: R
authors.lastname: Bousselaa
authors.affiliation: Department of Endocrinology Internal and External, Hedi Chaker University Hospital, Sfax, Tunisia.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abid
authors.affiliation: Department of Anatomy and Pathological Cytology, Habib Bourguiba University Hospital, Sfax, Tunisia.
authors.forename: Tahia
authors.initials: T
authors.lastname: Boudaouara
authors.affiliation: Laboratory of Analysis, Development and Food Safety, Research Group "Biotechnology and Pathology", National School of Engineers of Sfax, Sfax, Tunisia.
authors.forename: Hamadi
authors.initials: H
authors.lastname: Attia
authors.affiliation: Laboratory of Analysis, Development and Food Safety, Research Group "Biotechnology and Pathology", National School of Engineers of Sfax, Sfax, Tunisia.
authors.forename: Saloua
authors.initials: S
authors.lastname: Lassoued
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006111:Graves Disease / Q000150:complications*; D006151:Guanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D050031:Hashimoto Disease / Q000150:complications*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D006151:Guanosine; C046215:8-hydroxyguanosine
keywords: 8-OHdG; Graves's disease; Hashimoto thyroiditis; Papillary Thyroid Carcinoma