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MGMT expression in pituitary corticotroph adenomas and its relationship to clinical, pathological, and ultrastructural parameters in patients with Cushing’s disease
Folia Neuropathologica ( IF 2 ) Pub Date : 2021-01-11 , DOI: 10.5114/fn.2020.102438
Przemysław Witek 1 , Maria Maksymowicz 2 , Katarzyna Szamotulska 3 , Agata Piaścik 2 , Agnieszka Wojciechowska-Luźniak 1 , Aleksandra Stasiewicz 1 , Joanna Witek 4 , Grzegorz Zieliński 5
Affiliation  

Introduction
Transsphenoidal surgery is the treatment of choice in Cushing’s disease (CD), although even late recurrences occur in some patients. Low expression of O-6-methylguanine-DNA methyltransferase (MGMT) has been linked to a high risk of relapse in pituitary tumours, but the evidence for corticotroph adenomas is limited. Therefore, we investigated whether MGMT expression was associated with CD remission or clinicopathological markers of tumour aggressiveness among patients with corticotroph adenomas.

Material and methods
We included 72 consecutive patients (83% female, mean age ±SD: 44.15 ±15.15 years) with CD, who underwent transsphenoidal adenomectomy between 2012 and 2018. The invasiveness of corticotroph tumours was assessed based on the Knosp scale. Immunohistochemistry was used to analyse MGMT expression as well as the proliferation markers (Ki-67, p53, mitotic index). Electron microscopy was used to categorise tumours into densely or sparsely granulated. Early biochemical remission was evaluated in all patients 6 months after pituitary surgery.

Results
Early remission was observed in 47 (65%) patients 6 months after surgery. MGMT expression was > 75% in half of all tumours, < 25% in 14 tumours, and 25-50% or 50-75% in 11 tumours. Lower MGMT expression was associated with a larger tumour diameter (p = 0.001), higher adrenocorticotropic hormone (ACTH) concentration (p = 0.002), higher p53 expression (p = 0.026), and higher frequency of sparsely granulated corticotroph adenomas (p = 0.009). Low MGMT expression was significantly related to lower frequency of early clinical remission (p = 0.005).

Conclusions
MGMT predicted the outcomes of transsphenoidal surgery for CD. Pituitary corticotroph adenomas with low MGMT expression may be associated with increased invasiveness and poorer prognosis.



中文翻译:

库欣病患者垂体促肾上腺皮质激素腺瘤中MGMT的表达及其与临床、病理和超微结构参数的关系

介绍
经蝶窦手术是库欣病 (CD) 的首选治疗方法,尽管某些患者甚至会出现晚期复发。O-6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)的低表达与垂体肿瘤复发的高风险有关,但促肾上腺皮质激素腺瘤的证据有限。因此,我们研究了 MGMT 表达是否与促肾上腺皮质激素腺瘤患者的 CD 缓解或肿瘤侵袭性的临床病理学标志物相关。

材料与方法
我们纳入了 2012 年至 2018 年间接受经蝶窦腺切除术的 72 名连续 CD 患者(83% 女性,平均年龄 ±SD:44.15 ±15.15 岁)。根据 Knosp 量表评估促肾上腺皮质激素肿瘤的侵袭性。免疫组织化学用于分析 MGMT 表达以及增殖标志物(Ki-67、p53、有丝分裂指数)。电子显微镜用于将肿瘤分类为密集或稀疏颗粒。在垂体手术后 6 个月,对所有患者的早期生化缓解进行了评估。

结果
术后 6 个月,47 名(65%)患者观察到早期缓解。MGMT 表达在所有肿瘤的一半中 > 75%,在 14 个肿瘤中 < 25%,在 11 个肿瘤中为 25-50% 或 50-75%。较低的 MGMT 表达与较大的肿瘤直径(p = 0.001)、较高的促肾上腺皮质激素(ACTH)浓度(p = 0.002)、较高的 p53 表达(p = 0.026)和稀疏颗粒状促肾上腺皮质激素腺瘤的频率较高(p = 0.009)相关)。低 MGMT 表达与早期临床缓解的较低频率显着相关(p = 0.005)。

结论
MGMT 可预测 CD 经蝶窦手术的结果。MGMT 低表达的垂体促肾上腺皮质激素腺瘤可能与侵袭性增加和预后较差有关。

更新日期:2021-01-12
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