Immunohistochemical Assessment of O⁶-Methylguanine-DNA Methyltransferase (MGMT) and Its Relationship with p53 Expression in Endometrial Cancers

Abstract

O6-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein, the loss of MGMT expression was commonly known due to hypermethylation of CpG islands in its promoter region. Overexpression of p53 protein may be associated with downregulated MGMT expression in brain tumors. The aims of this study were to investigate the role of MGMT expression loss and its correlation with p53 overexpression in endometrial cancers. MGMT and p53 expression was examined in formalin-fixed, paraffin-embedded tissues from 36 endometrial cancer cases using immnunohistochemical staining. The loss of MGMT expression was detected in 11 (30.6%) out of the 36 endometrial cancers and p53 immunoreactivity was detected in 23 (63.9%) out of the 36 endometrial cancers. Ten (90.9%) of the 11 cases with negative MGMT immunoreactivity showed positive p53 expression, so the loss of MGMT expression was significantly associated with the p53 overexpression (P=0.03). These findings suggest that the loss of MGMT expression may be one of factors capable of p53 overexpression in endometrial cancer. Further studies are needed to define the relation between MGMT and p53 for examining the mechanisms of tissue-specific MGMT expression.

Sulforaphane reverses chemo-resistance to temozolomide in glioblastoma cells by NF-κB-dependent pathway downregulating MGMT expression

“…Several transcription factors have been suggested to be involved in the complex process of MGMT transcriptional regulation, including p53, NF-κB, HIF-1α, and AP-1 (15)(16)(17). NF-κB is a family of direct transcription factors which can bind to specific DNA sequences in target genes involving in immunoregulation, inflammation, growth, carcinogenesis and apoptosis (18,19).…”

Genomic Profiling of Chronic Myelogenous Leukemia: Basic and Clinical Approach

“…Imatinib treatment has clearly improved the prognosis for CML patients, especially in the CP, the occurrence of relapse,1,2 resistance,23,33,34 and the requirement for continued therapy 35,36. Here, we examine the stem cell origin of CML, and then discuss the recent findings that the Hedgehog (Hh) pathway contributes to the survival and expansion of BCR-ABL leukemic stem cells 37,38.…”

“…The transition from the chronic to the advanced phase of CML involves distinct changes in gene expression that predict increased activation of the WNT/β-catenin pathway, as well as deregulated expression of several transcriptional regulators, including JunB, Fos, and PRAME. 18 Imatinib treatment has clearly improved the prognosis for CML patients, especially in the CP, the occurrence of relapse, 1 , 2 resistance, 23 , 33 , 34 and the requirement for continued therapy. 35 , 36 Here, we examine the stem cell origin of CML, and then discuss the recent findings that the Hedgehog (Hh) pathway contributes to the survival and expansion of BCR-ABL leukemic stem cells.…”

MGMT Immunohistochemical Expression in Colorectal Carcinoma and its Correlation with Tumor Progression

“…Furthermore, MGMT epigenetic silencing is linked to its lack of expression through the methylation process. Loss of MGMT expression has a significant role in carcinogenesis in various tumors as gliomas, non-small cell lung carcinoma, and diffuse large B-cell lymphoma [5], [6], [7]. Temozolomide (TMZ), an alkylating chemotherapeutic drug, is widely used to treat glioblastoma patients.…”