Implications of MGMT methylation status in pituitary adenoma

Arya, Sneha; Majaid, M.A.; Shwetha, S; Sravani, K.; Arivazhagan, Arimappamagan; Somanna, Sampath; Santosh, Vani

doi:10.1016/j.prp.2014.02.010

Cited by 10 publications

(10 citation statements)

References 19 publications

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“…Considering low levels of Ki67 LI, methylation-depending differences were also hardly detectable in further studies. Thus, similar to us, Quian et al reported an increased median Ki67 LI in patients with methylation of RASSF1A as compared to patients lacking DNA methylation (1.6 vs. 1.2 %, respectively), while MGMT promoter methylation in PA was found to be independent of Ki67 LI in another series [3,28].…”

Section: Discussionsupporting

confidence: 81%

“…Interestingly, although several studies previously detected methylation in other promoter regions (e.g., MGMT, KCNAB2, SFRP4, WIF1, RASSF3, CDKN2C, FGFR2, RB1, CDKN2B, p16, LGALS3) in 30-70 % of PA, correlation to patients' outcome is sparsely investigated [8,26,[29][30][31][32][33][34][35]. In 2014, Arya et al reported MGMT promoter methylation in 40 % of PA but without prognostic impact [3]. Further studies also revealed methylation of the CDH1, CDH13, and GSTP1 promoter and numerous genes, e.g., FLT1 and SLIT3, to be associated with tumor invasiveness [8,25,36] and malignancy [37], and therefore basically indirectly related to worse prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…Rather than alterations in genomic DNA, epigenetic silencing and activation of numerous genes are considered to play a major role in tumorigenesis of PA. Thus, methylation of genomic DNA (e.g., CDKN2A, FGFR2, CASP8, RB1, p73, MGMT, and TIMP3) and CpGrich promoter regions (CpG islands) with subsequent gene silencing has been reported in various studies [3][4][5][6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 97%

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hTERT promoter methylation in pituitary adenomas

et al. 2015

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Telomerase reverse transcriptase (TERT) expression is a hallmark in tumorigenesis and upregulated due to mutations and methylation of the human (h)TERT promoter. As mutations are rare but methylation is common in pituitary adenomas (PA), we determined promoter methylation and its clinical impact in 85 primary and 15 recurrent PA by methylation-specific PCR. 40 females (47%) and 45 males (53%) with a median age of 53 years harboring micro-, macro-, and giant adenomas in 12, 82, and 6% were included (prolactinomas, corticotroph, somatotroph, gonadotroph, thyreotroph, plurihormonal, and null cell adenomas in 11, 18, 10, 29, 1, 10, and 21%, respectively). In primary diagnosed tumors, methylation rate was 27% and higher in males than in females (40 vs. 13%, p = 0.001) after uni- and multivariate analyses. Methylation differed among PA subtypes (0-42%, p = n.s.) and was not significantly correlated with tumor size, cavernous sinus invasion, or serum hormone levels. Ki67 labeling index and recurrence (N = 16, 19%) were independent of methylation. In recurrent tumors, methylation was similar to primary PA (N = 5/15, 33%) and remained unchanged along follow-up. Thus, while being commonly observed in PA, hTERT promoter methylation is stable along follow-up and independent of most clinical variables, PA subtype, proliferation, and without prognostic value.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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hTERT promoter methylation in pituitary adenomas

et al. 2015

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“…Recently, the upregulation of mitogen-activated protein kinase has also been reported in gangliogliomas [37]. Moreover, when the methylation status of O(6)-methylguanine DNA methyltransferase (MGMT) was examined in pituitary adenomas, the degree of MGMT expression appeared to be related to therapeutic responses to temozolomide [1,24,26]. MGMT protein expression was also implicated as a prognostic factor for patients with low-grade gangliogliomas [11].…”

Section: Discussionmentioning

confidence: 99%

Ganglion cell tumours in the sella turcica in close morphological connection with pituitary adenomas

Matyja

Maksymowicz²,

Grajkowska³

et al. 2015

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“…The lower expression of MGMT is reportedly predictive of responsiveness to TMZ [19,20]. And several studies report that MGMT expression is associated with PA patients' prognoses [21].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of 06-methylguanine-DNA methyltransferase expression in children and adolescent pituitary adenoma

Shen¹,

Yang²,

Yang³

et al. 2020

Preprint

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BackgroundTemozolomide can be used in the treatment of pituitary adenoma. Its efficacy can be evaluated by the expression of 06-methylguanine-DNA methyltransferase (MGMT). However, the previous study population was mainly adult. This study was the first to evaluate the expression of MGMT in children and adolescents with pituitary adenomas.MethodsThe clinical features and biological characteristics of 38 cases of pituitary adenoma in children and adolescents were analyzed retrospectively. The expression of MGMT, Ki-67, p53 was marked by immunohistochemical staining.ResultsIn this cohort, the expression of MGMT protein is 16/38 (42.11%). The low expression rate of MGMT in children and adolescent somatotroph adenomas was only 11.11%, which was much lower than that of adults. Ki-67 expression range of 1% -10%（mean 4.24 ± 2.71%）. The positive rate of p53 was 22/38 (57.89%). The statistical analysis showed that the expression of MGMT was related to the diameter of the tumor (P=0.01), the diameter of the tumor was large, and the expression of MGMT was high. The expression of MGMT was not associated with age, sex, tumor type, invasiveness, texture, apoplexy, recurrence, and expression of p53 and Ki-67.ConclusionSomatotroph adenomas, large-diameter children and adolescent pituitary adenomas may be not suitable for temozolomide treatment. To determine whether temozolomide responds to salvage therapy in children and adolescents with pituitary adenomas, MGMT expression should be assessed in all pituitary adenomas, the time span between specimen collection and temozolomide treatment needs to be considered because of the instability of MGMT protein expression.

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Implications of MGMT methylation status in pituitary adenoma

Cited by 10 publications

References 19 publications

hTERT promoter methylation in pituitary adenomas

hTERT promoter methylation in pituitary adenomas

Ganglion cell tumours in the sella turcica in close morphological connection with pituitary adenomas

Evaluation of 06-methylguanine-DNA methyltransferase expression in children and adolescent pituitary adenoma

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