垂体促肾上腺皮质腺瘤中 O-6-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）免疫组化表达。

O-6-methylguanine-DNA methyltransferase (MGMT) immunohistochemical expression in pituitary corticotroph adenomas.

机构信息

Department of Laboratory Medicine, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.

出版信息

Neurosurgery. 2012 Feb;70(2):491-6; discussion 496. doi: 10.1227/NEU.0b013e318230ac63.

DOI:10.1227/NEU.0b013e318230ac63

PMID:21822153

Abstract

BACKGROUND

O-6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that counteracts chemotherapeutic cytotoxicity of alkylating agents such as temozolomide. Low levels of MGMT expression have been shown to correlate with longer survival in glioma patients treated with temozolomide. The same is true in pituitary adenomas.

OBJECTIVE

We investigated the immunohistochemical expression of MGMT in a variety of corticotroph adenoma subtypes to determine the potential utility of temozolomide as a therapeutic agent.

METHODS

The tumors consisted of 40 cases of adrenocorticotropin-secreting pituitary tumors in Cushing disease, 12 Crooke cell adenomas, and 7 subtype I silent corticotroph adenomas. Staining for MGMT was assessed by light microscopy; nuclear reactivity was estimated semiquantitatively as present in < 10%, 10% to 25%, 25% to 50%, 50% to 75%, and > 75% of cells.

RESULTS

Immunoexpression showed no correlation with patient age, sex, tumor size, invasiveness, or recurrence in patients with Cushing disease. Among adrenocorticotropin-secreting adenomas associated with Cushing disease, most invasive (60%) and recurrent (86%) tumors showed low MGMT immunopositivity, defined as < 25%. Most (75%) Crooke cell adenomas exhibited an MGMT immunoreactivity of ≤ 50%. All subtype I silent corticotroph adenomas showed < 10% MGMT staining.

CONCLUSION

Our descriptive findings of low MGMT expression in adrenocorticotropin-producing pituitary adenomas, particularly aggressive tumors, suggest that they may be suitable candidates for temozolomide therapy.

摘要

背景

O-6-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）是一种 DNA 修复酶，可抵抗替莫唑胺等烷化剂的化疗细胞毒性。在接受替莫唑胺治疗的胶质瘤患者中，MGMT 表达水平较低与生存时间延长相关。这同样适用于垂体腺瘤。

目的

我们研究了各种促肾上腺皮质激素分泌腺瘤亚型中 MGMT 的免疫组织化学表达，以确定替莫唑胺作为治疗剂的潜在用途。

方法

该肿瘤包括 40 例库欣病中的促肾上腺皮质激素分泌性垂体瘤、12 例 Crooke 细胞腺瘤和 7 例 I 型无功能型促肾上腺皮质激素分泌性腺瘤。通过光学显微镜评估 MGMT 的染色情况；核反应性以<10%、10%-25%、25%-50%、50%-75%和>75%的细胞存在进行半定量估计。

结果

免疫表达与库欣病患者的年龄、性别、肿瘤大小、侵袭性或复发均无相关性。在与库欣病相关的促肾上腺皮质激素分泌性腺瘤中，大多数侵袭性（60%）和复发性（86%）肿瘤表现出低 MGMT 免疫阳性，定义为<25%。大多数（75%）Crooke 细胞腺瘤表现出≤50%的 MGMT 免疫反应性。所有 I 型无功能型促肾上腺皮质激素分泌性腺瘤的 MGMT 染色均<10%。