title: Expression of DNA repair proteins MSH2, MLH1 and MGMT in human benign and malignant thyroid lesions: an immunohistochemical study.
abstract: BACKGROUND
  DNA repair is a major defense mechanism, which contributes to the maintenance of genetic sequence, and minimizes cell death, mutation rates, replication errors, DNA damage persistence and genomic instability. Alterations in the expression levels of proteins participating in DNA repair mechanisms have been associated with several aspects of cancer biology. The present study aimed to evaluate the clinical significance of DNA repair proteins MSH2, MLH1 and MGMT in benign and malignant thyroid lesions.
  
  
  METHODS
  MSH2, MLH1 and MGMT protein expression was assessed immunohistochemically on paraffin-embedded thyroid tissues from 90 patients with benign and malignant lesions.
  
  
  RESULTS
  The expression levels of MLH1 was significantly upregulated in cases with malignant compared to those with benign thyroid lesions (p = 0.038). The expression levels of MGMT was significantly downregulated in malignant compared to benign thyroid lesions (p = 0.001). Similar associations for both MLH1 and MGMT between cases with papillary carcinoma and hyperplastic nodules were also noted (p = 0.014 and p = 0.026, respectively). In the subgroup of malignant thyroid lesions, MSH2 downregulation was significantly associated with larger tumor size (p = 0.031), while MLH1 upregulation was significantly associated with the presence of lymphatic and vascular invasion (p = 0.006 and p = 0.002, respectively).
  
  
  CONCLUSIONS
  Alterations in the mismatch repair proteins MSH2 and MLH1 and the direct repair protein MGMT may result from tumor development and/or progression. Further studies are recommended to draw definite conclusions on the clinical significance of DNA repair proteins in thyroid neoplasia.
authors.affiliation: Department of Forensic Medicine and Toxicology, Medical School, University of Athens, Athens, Greece.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Giaginis
authors.forename: Christina
authors.initials: C
authors.lastname: Michailidi
authors.forename: Vasileios
authors.initials: V
authors.lastname: Stolakis
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Alexandrou
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Tsourouflis
authors.forename: Jerzy
authors.initials: J
authors.lastname: Klijanienko
authors.forename: Ioanna
authors.initials: I
authors.lastname: Delladetsima
authors.forename: Stamatios
authors.initials: S
authors.lastname: Theocharis
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D015254:DNA Modification Methylases / Q000378:metabolism*; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes