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

Abstract

SummaryBackgroundDNA 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/MethodsMSH2, MLH1 and MGMT protein expression was assessed immunohistochemically on paraffin-embedded thyroid tissues from 90 patients with benign and malignant lesions.ResultsThe 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).ConclusionsAlterations 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.

DNA repair proteins may differentiate papillary thyroid cancer from chronic lymphocytic thyroiditis and nodular colloidal goiter

“…Papillary carcinoma cases also show an increased incidence of low MGMT compared to hyperplastic nodules. Moreover, low MGMT is associated with large tumor size in thyroid cancer cases 6 . In addition, Schagdarsureng reported that MGMT hypermethylation is occurred priorly compared to differentials in undifferentiated thyroid carcinomas 9 .…”

“…It is known that inherited or acquired deficiencies in DNA repair proteins can lead to deleterious mutations, cell death associated with cancer development, differentiation, and progression. In particular, changes in the expression levels and polymorphisms of DNA repair genes have been considered responsible for thyroid carcinogenesis 6 . There are limited studies in the literature on the importance of IHC expressions of MSH2, MLH1, and MGMT in the differentiation of benign and malignant thyroid lesions.…”

“…Prepared sections were qualitatively examined by an impartial pathologist, taking into account the staining method under the trinocular light microscope (Olympus BX-51). The evaluation method in the preparation is based on a previous study and given below 6 .…”

“…Among them, MMR proteins such as MSH2 (Mut-S-Homologin-2) and MLH1 (Mut-L-Homologin-1) have been implicated in the development and progression of various head and neck neoplasms, including the thyroid. Loss of MGMT expression has been associated with hepatocellular, lung, stomach, and breast carcinomas, aggressive tumor behavior, and progression in various types of neoplasia, including the esophagus 6 . However, available data evaluating the immunohistochemical expression of MSH2, MLH1, and MGMT in benign and malignant thyroid lesions have so far been insufficient.…”

Investigation of DNA repair-related SNPs underlying susceptibility to papillary thyroid carcinoma reveals MGMT as a novel candidate gene in Belarusian children exposed to radiation

“…Nevertheless, a link between MGMT and thyroid cancer had already been established in few studies. First, it was shown that expression level of MGMT protein was significantly downregulated in malignant compared to benign thyroid lesions [ 47 ]. Secondly, the methylation status of MGMT has also been investigated in thyroid neoplasia [ 48 , 49 ].…”