Cancer Res Treat.  2010 Jun;42(2):95-100.

Role of Loss of O(6)-Methylguanine DNA Methyltransferase (MGMT) Expression in Non-Small Cell Lung Carcinomas (NSCLCs): with Reference to the Relationship with p53 Overexpression

• Myong NH

Abstract

PURPOSE
Functional inactivation of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene has been demonstrated as loss of MGMT protein and suggested that it plays an important role in primary human neoplasia, including lung cancer. It has also been reported to be associated with the G : C-->A : T transition mutation in the p53 gene of lung cancer. The aims of this study were to investigate the role of MGMT expression loss and its prognostic significance in non-small cell lung carcinomas (NSCLCs), and its correlation with p53 overexpression as well as influence on patient survival.
MATERIALS AND METHODS
112 surgically resected NSCLC specimens were reviewed by medical records for their clinicopathologic variables. Their tissue microarray blocks were immunostained with anti-human MGMT and p53 primary antibodies. Correlation between MGMT loss and the clinicopathologic prognostic factors, including p53 overexpression and the single or combined actions of MGMT loss and p53 overexpression on patient survival were statistically analyzed by SPSS15.0.
RESULTS
Reduced or absent MGMT expression was found in 48 of 112 NSCLCs (43%), and significantly associated with nodal metastasis and squamous or undifferentiated cell types. Loss of MGMT expression was correlated with p53 overexpression in adenocarcinomas, but not in overall NSCLCs. Its solitary or combined actions with p53 overexpression did not have influence on patient survival.
CONCLUSION
Loss of MGMT expression is a relatively common event in NSCLCs and significantly associated with nodal metastasis and p53 overexpression, suggesting that it may play a major role in pulmonary carcinogenesis, and also in disease progression of NSCLCs.

Keyword

MGMT protein; Non-small-cell lung carcinomas (NSCLCs); Carcinogenesis; Disease progression; p53 protein

MeSH Terms

Adenocarcinoma
Antibodies
Disease Progression
DNA
Genes, p53
Guanine
Humans
Lung
Lung Neoplasms
Medical Records
Neoplasm Metastasis
O(6)-Methylguanine-DNA Methyltransferase
Antibodies
DNA
Guanine
O(6)-Methylguanine-DNA Methyltransferase

Figure

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  Fig. 1 A normal matched lung showing positive nuclear immunoreactivity for MGMT protein in bronchial epithelial and stromal cells (×200).

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  Fig. 2 Poorly differentiated squamous carcinoma reveals loss of MTMT immunoreactivity compared to adjacent stromal lymphocytes showing retained nuclear MGMT-immunoreactivity (×200).

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  Fig. 3 A moderately differentiated squamous carcinoma shows diffuse nuclear immunoreactivity for MGMT protein in both tumor and normal cell components (×200).

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  Fig. 4 A case of squamous carcinoma showing no nuclear immunoreactivity for MGMT protein (A) and, simultaneously diffuse nuclear immunostaining for p53 protein (B) in the tumor cells (×200).

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