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O-甲基鸟嘌呤-DNA甲基转移酶(MGMT)甲基化状态在垂体腺瘤中的意义

Implications of MGMT methylation status in pituitary adenoma.

作者信息

Arya Sneha, Majaid M A, Shwetha S D, Sravani K, Arivazhagan A, Sampath S, Santosh V

机构信息

Department of Neuropathology, National Institute of Mental Health and NeuroSciences, Bangalore, India.

Department of Neurosurgery, National Institute of Mental Health and NeuroSciences, Bangalore, India.

出版信息

Pathol Res Pract. 2014 Jul;210(7):407-11. doi: 10.1016/j.prp.2014.02.010. Epub 2014 Mar 12.

DOI:10.1016/j.prp.2014.02.010
PMID:24690322
Abstract

BACKGROUND

Very little literature exists on frequency of MGMT methylation status in pituitary adenoma. We assessed the frequency of MGMT methylation and protein expression in pituitary adenoma and correlated with patients' age group and prognosis.

METHODS

Tumor tissues from 30 patients with pituitary adenoma were evaluated for MGMT promoter methylation status by methylation specific PCR method. All tumors were also immunostained with MIB-1, anti-p53 and anti-MGMT antibodies.

RESULTS

MGMT methylation status was noted in 40% of cases (7/20 non-functioning adenomas and 5/10 functioning adenomas). MGMT protein expression on IHC was noted in 72.2% of unmethylated tumors, while only 41.6% of methylated tumors demonstrated protein expression. The mean labeling index of MGMT protein was higher in unmethylated tumors as compared to the methylated group, though the difference was not statistically significant (18.6% vs 8.8%; p=0.131). Tumor regrowth occurred in four unmethylated tumors as compared to none in methylated group. Even though there was no correlation between patient age and MGMT methylation status (p=0.823), we noted that the frequency of methylation in middle age patients (between 30 and 59 yrs) was 64.7%, which was higher compared to other age groups.

CONCLUSION

This is the first study from India showing MGMT promoter methylation status with protein expression in pituitary adenoma. We noted that tumor regrowth was higher in unmethylated tumors.

摘要

背景

关于垂体腺瘤中MGMT甲基化状态的频率,相关文献极少。我们评估了垂体腺瘤中MGMT甲基化和蛋白表达的频率,并与患者年龄组及预后进行关联分析。

方法

采用甲基化特异性PCR方法对30例垂体腺瘤患者的肿瘤组织进行MGMT启动子甲基化状态评估。所有肿瘤还采用MIB-1、抗p53和抗MGMT抗体进行免疫染色。

结果

40%的病例存在MGMT甲基化状态(7/20例无功能腺瘤和5/10例功能性腺瘤)。免疫组化显示,72.2%的未甲基化肿瘤有MGMT蛋白表达,而甲基化肿瘤中只有41.6%有蛋白表达。未甲基化肿瘤中MGMT蛋白的平均标记指数高于甲基化组,尽管差异无统计学意义(18.6%对8.8%;p=0.131)。4例未甲基化肿瘤出现肿瘤复发,而甲基化组无复发。尽管患者年龄与MGMT甲基化状态之间无相关性(p=0.823),但我们注意到中年患者(30至59岁)的甲基化频率为64.7%,高于其他年龄组。

结论

这是印度第一项显示垂体腺瘤中MGMT启动子甲基化状态与蛋白表达的研究。我们注意到未甲基化肿瘤的肿瘤复发率更高。

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