[Morphological predictors of the efficacy of mitotane therapy in adrenocortical cancer].

Q4 Medicine
A V Tkachuk, D G Beltsevich, E E Porubayeva, L S Urusova
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引用次数: 1

Abstract

Background: Adrenocortical cancer (ACC) is an orphan malignant tumor of the adrenal cortex with a predominantly poor prognosis and an aggressive clinical course. Nowadays, mitotane is a non-alternative drug in the treatment of ACC. The search for prognostic parameters that determine the sensitivity of ACC to ongoing treatment is currently an urgent task. Expression levels of the large subunit of ribonucleotide reductase M1 (RRM1), cytochrome P450 2W1 (CYP2W1), and sterol- O-acyltransferase-1 (SOAT1) are considered as potential predictors of response to mitotane therapy.

Aim: To assess the immunohistochemical expression of RRM1, CYP2W1 and SOAT1 in ACC as markers of clinical outcomes and response to the therapy with mitotane.

Materials and methods: The study included 62 patients older than 17 years of age with a diagnosis of ACC confirmed histologically and immunohistochemically. Mitotane therapy was initiated in 29 patients in the postoperative period, 33 patients were under dynamic observation without concomitant drug treatment. Antibodies to RRM1, CYP2W1, SOAT1 were used diluted in accordance with recommendations of firms-manufacturers for immunohistochemical detection.

Results: In the group of patients with low and moderate RRM1, CYP2W1 and SOAT1 immunoreactivity in the tumor and no antitumor therapy, a better DFS was noted (p=0.037, p=0.020 and p=0.001, respectively) compared to the group of patients receiving mitotane therapy at this level of marker expression. With high immunoreactivity of the markers, no statistically significant differences in DFS were found.

Conclusion: Consistent with the findings in our study, low expression of RRM1, CYP2W1 and SOAT1 was associated with worse DFS with antitumor therapy. The results of the work indicate the need to assess the levels of immunoreactivity of these markers in patients with ACC before starting treatment with mitotane in order to predict the efficiency of therapy.

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Abstract Image

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[米托坦治疗肾上腺皮质癌疗效的形态学预测因子]。
背景:肾上腺皮质癌(ACC)是一种罕见的肾上腺皮质恶性肿瘤,主要预后不良,临床病程具有侵袭性。目前,米托坦是治疗ACC的非替代药物。寻找决定ACC对持续治疗敏感性的预后参数目前是一项紧迫的任务。核糖核苷酸还原酶M1 (RRM1)、细胞色素P450 2W1 (CYP2W1)和甾醇- o -酰基转移酶1 (SOAT1)的表达水平被认为是对米托坦治疗反应的潜在预测因子。目的:评价ACC中RRM1、CYP2W1和SOAT1的免疫组化表达作为临床结局和对米托坦治疗反应的标志。材料和方法:本研究纳入62例年龄大于17岁且经组织学和免疫组织化学诊断为ACC的患者。29例患者术后开始米托坦治疗,33例患者动态观察,未合并药物治疗。抗体RRM1, CYP2W1, SOAT1按照公司-制造商的建议稀释用于免疫组织化学检测。结果:肿瘤中RRM1、CYP2W1和SOAT1免疫反应性低、中等且未接受抗肿瘤治疗的患者,在该标记物表达水平下,与接受米托坦治疗的患者相比,DFS更好(p=0.037、p=0.020和p=0.001)。标记物免疫反应性高,DFS差异无统计学意义。结论:与本研究结果一致,RRM1、CYP2W1和SOAT1低表达与抗肿瘤治疗后DFS恶化相关。研究结果表明,在开始使用米托坦治疗前,有必要评估ACC患者中这些标志物的免疫反应性水平,以预测治疗效果。
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来源期刊
Problemy endokrinologii
Problemy endokrinologii Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
1.40
自引率
0.00%
发文量
59
期刊介绍: Since 1955 the “Problems of Endocrinology” (or “Problemy Endocrinologii”) Journal publishes timely articles, balancing both clinical and experimental research, case reports, reviews and lectures on pressing problems of endocrinology. The Journal is aimed to the most topical issues of endocrinology: to chemical structure, biosynthesis and metabolism of hormones, the mechanism of their action at cellular and molecular level; pathogenesis and to clinic of the endocrine diseases, new methods of their diagnostics and treatment. The Journal: features original national and foreign research articles, reflecting world endocrinology development; issues thematic editions on specific areas; publishes chronicle of major international congress sessions and workshops on endocrinology, as well as state-of-the-art guidelines; is intended for scientists, endocrinologists diabetologists and specialists of allied trade, general practitioners, family physicians and pediatrics.
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