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

Myong, Na Hye

doi:10.4143/crt.2010.42.2.95

Cited by 6 publications

(3 citation statements)

References 12 publications

(11 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although p53 is widely mutated in many human cancers, it is rarely mutated in pituitary adenomas [ 25 ]. In the present study, almost 40 % of the samples had 5 % or more positive staining of p53, which was negatively associated with MGMT immunoexpression, as has been confirmed in other human cancers, including breast, lung, and pancreatic [ 15 , 16 ]. Moreover, MGMT suppression was associated with p53 activation, and accumulation of p53 increased the cell response to alkylation agents [ 17 – 20 ].…”

Section: Discussionsupporting

confidence: 83%

See 1 more Smart Citation

Expression profiling of O6 methylguanine-DNA-methyl transferase in prolactinomas: a correlative study of promoter methylation and pathological features in 136 cases

Jiang

Mao

et al. 2015

BMC Cancer

View full text Add to dashboard Cite

BackgroundLow-level expression of O6 methylguanine-DNA-methyl transferase (MGMT) prolactinomas has been noted previously in case reports, although what modulates MGMT expression remains unclear. This study therefore aimed to delineate the factors regulating MGMT expression in prolactinomas.MethodsWe retrospectively reviewed 136 prolactinoma patients who were treated in our center between January 2000 and September 2013. Expression of MGMT, Ki-67, and p53 protein were examined by immunohistochemical staining, and MGMT promoter methylation evaluated with methylation-specific PCR.ResultsMGMT immunopositivity was <25 % in 106/136 tumor specimens (77.94 %). MGMT immunoexpression was positively correlated with age (r = 0.251, p = 0.003), but inversely correlated with p53 staining (r = −0.153, p = 0.021). Moreover, reduced MGMT expression was more frequent in atypical prolactinomas (p = 0.044). Methylated MGMT promoter was confirmed in 10/46 specimens (21.7 %), all of which had low level or absent MGMT staining. Both p53 protein (r = −0.33, p = 0.025) and promoter methylation (r = −0.331, p = 0.025) were negatively associated with MGMT expression. Multivariate logistic analysis indicated that age (odds ratio [OR] = 1.127. 95 % confidence interval [CI] 1.027–1.236, p = 0.012) and p53 (OR = 0.116. 95 % CI 0.018–0.761, p = 0.025) staining were independent determents of MGMT expression.ConclusionsThe majority of prolactinomas, especially atypical prolactinomas, showed low-level or no MGMT immunoexpression, providing a rationale for the utility of temozolomide as an alternative to managing prolactinomas. In summary, epigenetic and transcriptional regulation are involved in silencing MGMT expression.

show abstract

Section: Discussionsupporting

confidence: 83%

“…The role of p53 in modulating MGMT expression is controversial. Several studies have suggested an inverse correlation of p53 with MGMT expression [ 15 , 16 ]. However, it has also been shown that accumulation of p53 protein suppresses MGMT expression and promotes cell sensitivity to alkylating agents [ 17 – 20 ].…”

Section: Introductionmentioning

confidence: 99%

Expression profiling of O6 methylguanine-DNA-methyl transferase in prolactinomas: a correlative study of promoter methylation and pathological features in 136 cases

Jiang

Mao

et al. 2015

BMC Cancer

View full text Add to dashboard Cite

show abstract

“…Myong reported that MGMT loss associated with p53 overexpression in lung cancers, especially adenocarcinomas. 14 Also, Osanai et al reported that expression of p53 may be associated with the regulation of MGMT expression in breast tumors, and that MGMT immunonegativity and p53 immunopositivity may be strong predictors of breast cancer survival. 15 However, other studies that wild-type p53 is accompanied by lower MGMT protein expression.…”

Section: Discussionmentioning

confidence: 99%

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

Lee

2013

J Cancer Prev

View full text Add to dashboard Cite

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.

show abstract

Relationship Between the Expression of O6-Methylguanine-DNA Methyltransferase (MGMT) and p53, and the Clinical Response in Metastatic Pancreatic Adenocarcinoma Treated with FOLFIRINOX

Vitellius

Eymerit-Morin

Fizanne³

et al. 2017

Clin Drug Investig

View full text Add to dashboard Cite

These preliminary findings suggest that for patients treated with FOLFIRINOX as a first-line treatment for metastatic pancreatic adenocarcinoma, the immunohistochemical evaluation of MGMT could not predict the clinical outcome; however, the survival was not significant probably because of the under-powered study (due to small sample size). A strong tumor expression of p53 is associated with a poor prognosis of OS.

show abstract

Role of Loss of O⁶-Methylguanine DNA Methyltransferase (MGMT) Expression in Non-Small Cell Lung Carcinomas (NSCLCs): with Reference to the Relationship with p53 Overexpression

Cited by 6 publications

References 12 publications

Expression profiling of O6 methylguanine-DNA-methyl transferase in prolactinomas: a correlative study of promoter methylation and pathological features in 136 cases

Expression profiling of O6 methylguanine-DNA-methyl transferase in prolactinomas: a correlative study of promoter methylation and pathological features in 136 cases

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

Relationship Between the Expression of O6-Methylguanine-DNA Methyltransferase (MGMT) and p53, and the Clinical Response in Metastatic Pancreatic Adenocarcinoma Treated with FOLFIRINOX

Contact Info

Product

Resources

About

Role of Loss of O6-Methylguanine DNA Methyltransferase (MGMT) Expression in Non-Small Cell Lung Carcinomas (NSCLCs): with Reference to the Relationship with p53 Overexpression

Cited by 6 publications

References 12 publications

Expression profiling of O6 methylguanine-DNA-methyl transferase in prolactinomas: a correlative study of promoter methylation and pathological features in 136 cases

Expression profiling of O6 methylguanine-DNA-methyl transferase in prolactinomas: a correlative study of promoter methylation and pathological features in 136 cases

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

Relationship Between the Expression of O6-Methylguanine-DNA Methyltransferase (MGMT) and p53, and the Clinical Response in Metastatic Pancreatic Adenocarcinoma Treated with FOLFIRINOX

Contact Info

Product

Resources

About

Role of Loss of O⁶-Methylguanine DNA Methyltransferase (MGMT) Expression in Non-Small Cell Lung Carcinomas (NSCLCs): with Reference to the Relationship with p53 Overexpression

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