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α-甲基酰基辅酶A消旋酶(AMACR,p504s)是一种用于区分恶性黑色素瘤与发育异常痣及黑素细胞痣的标志物。

α-Methylacyl-coenzyme A racemase (AMACR, p504s) is a marker to distinguish malignant melanomas from dysplastic nevi and melanocytic nevi.

作者信息

Abbas M, Ploch E M, Wehling J, Schipper E, Janciauskiene S, Kreipe H H, Jonigk D

机构信息

Institute of Pathology, Hannover medical School (MHH), Carl-Neuberg-Str. 1, 30625, Hannover, Germany,

出版信息

Tumour Biol. 2014 Dec;35(12):12015-20. doi: 10.1007/s13277-014-2500-1. Epub 2014 Aug 24.

DOI:10.1007/s13277-014-2500-1
PMID:25149154
Abstract

Routinely processed skin biopsies are still the mainstay for the diagnosis of melanocytic skin neoplasms (MSNs) and are considered the "gold standard" for individual patient management and clinical trials. The diagnostic challenge of melanocytic lesions of the skin prompts histopathologists to consider new diagnostic tools; among these, immunohistochemistry. We aimed to find putative new immunohistochemical markers, which can supplement the histological criteria used to detect dysplasia. In this immunohistochemical study, we chose a panel of promising biomarkers which could potentially differentiate between different MSN entities. These included α-methylacyl-coenzyme A racemase (AMACR; p504s), which is involved in the degradation of branched chained fatty acid derivates. We analysed a cohort of benign nevi and malignant melanomas. The design of the study included 78 melanocytic skin neoplasms (26 malignant melanomas and 52 benign nevi) in a tissue microarray. Immunohistochemistry of cyclin-dependent kinase inhibitor 2A (p16Ink4a), methylacyl-coenzyme A racemase (AMACR), cyclin D1, and E-cadherin was performed and assessed. We have observed that the p16Ink4a, AMACR, cyclin D1, and E-cadherin showed no exclusive staining for nevi or melanomas. However, a significant overexpression of AMACR was found in malignant melanomas compared to benign nevi. AMACR overexpression was also associated with an increased p16Ink4a staining. Our results suggest AMACR as an immunohistochemical marker for distinguishing malignant melanomas and dysplastic nevi from conventional melanocytic nevi.

摘要

常规处理的皮肤活检仍是诊断黑素细胞性皮肤肿瘤(MSN)的主要方法,被视为个体患者管理和临床试验的“金标准”。皮肤黑素细胞病变的诊断挑战促使组织病理学家考虑新的诊断工具,其中包括免疫组织化学。我们旨在寻找可能的新免疫组织化学标志物,以补充用于检测发育异常的组织学标准。在这项免疫组织化学研究中,我们选择了一组有前景的生物标志物,它们可能有助于区分不同的MSN实体。这些标志物包括α-甲基酰基辅酶A消旋酶(AMACR;p504s),它参与支链脂肪酸衍生物的降解。我们分析了一组良性痣和恶性黑色素瘤。研究设计包括在组织芯片中纳入78例黑素细胞性皮肤肿瘤(26例恶性黑色素瘤和52例良性痣)。对细胞周期蛋白依赖性激酶抑制剂2A(p16Ink4a)、甲基酰基辅酶A消旋酶(AMACR)、细胞周期蛋白D1和E-钙黏蛋白进行免疫组织化学检测并评估。我们观察到,p16Ink4a、AMACR、细胞周期蛋白D1和E-钙黏蛋白对痣或黑色素瘤均无特异性染色。然而,与良性痣相比,恶性黑色素瘤中AMACR有明显的过表达。AMACR过表达还与p16Ink4a染色增加有关。我们的结果表明,AMACR可作为一种免疫组织化学标志物,用于区分恶性黑色素瘤和发育异常痣与传统黑素细胞痣。

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本文引用的文献

1
Increased expression of α-methylacyl-coenzyme A racemase (AMACR; p504s) and p16 in distal hyperplastic polyps.α-甲基酰基辅酶 A 消旋酶(AMACR;p504s)和 p16 在远端增生性息肉中的表达增加。
Diagn Pathol. 2013 Oct 23;8:178. doi: 10.1186/1746-1596-8-178.
2
An assessment of the diagnostic criteria for sessile serrated adenoma/polyps: SSA/Ps using image processing software analysis for Ki67 immunohistochemistry.应用图像处理软件分析 Ki67 免疫组化评估无蒂锯齿状腺瘤/息肉的诊断标准:SSA/P。
Diagn Pathol. 2012 May 29;7:59. doi: 10.1186/1746-1596-7-59.
3
Up and downregulation of p16(Ink4a) expression in BRAF-mutated polyps/adenomas indicates a senescence barrier in the serrated route to colon cancer.
p16(Ink4a) 表达的上调和下调表明 BRAF 突变的息肉/腺瘤中存在锯齿途径通向结肠癌的衰老屏障。
Mod Pathol. 2011 Jul;24(7):1015-22. doi: 10.1038/modpathol.2011.43. Epub 2011 Mar 18.
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[Dysplastic melanocytic nevus].[发育异常性黑素细胞痣]
Duodecim. 2010;126(21):2492-501.
5
Immunohistochemical evaluation of p16INK4A, E-cadherin, and cyclin D1 expression in melanoma and Spitz tumors.黑色素瘤和 Spitz 肿瘤中 p16INK4A、E-钙黏蛋白和细胞周期蛋白 D1 的免疫组织化学评估。
Am J Clin Pathol. 2010 Mar;133(3):370-9. doi: 10.1309/AJCP52YVYCTLUOPI.
6
Involvement of E-cadherin, beta-catenin, Cdc42 and CXCR4 in the progression and prognosis of cutaneous melanoma.E-钙黏蛋白、β-连环蛋白、Cdc42和CXCR4在皮肤黑色素瘤进展及预后中的作用
Br J Dermatol. 2007 Dec;157(6):1212-6. doi: 10.1111/j.1365-2133.2007.08246.x. Epub 2007 Oct 26.
7
Serrated polyps of the large intestine.大肠锯齿状息肉
Semin Diagn Pathol. 2005 Nov;22(4):301-8. doi: 10.1053/j.semdp.2006.04.003.
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Malignant melanoma: genetics and therapeutics in the genomic era.恶性黑色素瘤:基因组时代的遗传学与治疗学
Genes Dev. 2006 Aug 15;20(16):2149-82. doi: 10.1101/gad.1437206.
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Importance of P-cadherin, beta-catenin, and Wnt5a/frizzled for progression of melanocytic tumors and prognosis in cutaneous melanoma.P-钙黏蛋白、β-连环蛋白以及Wnt5a/卷曲蛋白在黑素细胞肿瘤进展及皮肤黑色素瘤预后中的重要性
Clin Cancer Res. 2005 Dec 15;11(24 Pt 1):8606-14. doi: 10.1158/1078-0432.CCR-05-0011.
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Using an AMACR (P504S)/34betaE12/p63 cocktail for the detection of small focal prostate carcinoma in needle biopsy specimens.使用AMACR(P504S)/34βE12/p63联合检测针吸活检标本中的小灶性前列腺癌。
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