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25 February 2011

Expression of DNA repair proteins MSH2, MLH1 and MGMT in human benign and malignant thyroid lesions: An immunohistochemical study

Constantinos GiaginisABDE, Christina MichailidiB, Vasileios StolakisB, Paraskevi AlexandrouBD, Gerasimos TsourouflisF, Jerzy KlijanienkoD, Ioanna DelladetsimaBD, Stamatios TheocharisADFG

DOI: 10.12659/MSM.881444

Med Sci Monit 2011; 17(3): BR81-90

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.
Material/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.

Keywords: Nuclear Proteins - metabolism, MutS Homolog 2 Protein - metabolism, DNA Repair Enzymes - metabolism, DNA Repair, DNA Modification Methylases - metabolism, Adaptor Proteins, Signal Transducing - metabolism, Thyroid Neoplasms - pathology, Tumor Suppressor Proteins - metabolism

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