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丝氨酸/苏氨酸激酶 1(Plk1)在皮肤 T 细胞淋巴瘤中的作用。

Polo-like kinase 1 (Plk1) in cutaneous T-cell lymphoma.

机构信息

Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.

出版信息

Br J Dermatol. 2011 Apr;164(4):814-21. doi: 10.1111/j.1365-2133.2010.10128.x. Epub 2011 Jan 28.

Abstract

BACKGROUND

Polo-like kinase 1 (Plk1) has multiple functions throughout mitosis. Plk1 levels are high in a number of cancers and haematological malignancies while being low in most differentiated tissues.

OBJECTIVES

To assess the immunoreactivity of Plk1 in cutaneous T-cell lymphoma (CTCL) as a potential therapeutic target, to differentiate Plk1 levels among lesion types and to compare the detection level of Plk1 in fresh frozen (f) vs. paraffin-embedded (p) tissue.

METHODS

Immunohistochemical staining of CTCL skin lesions with anti-Plk1 antibody was performed in a total of 65 biopsies from 49 patients with CTCL. Both f and p tissue was available for comparison in 46 biopsies.

RESULTS

Tumour-stage CTCL lesions displayed significantly more Plk1 (mean f 7·7%, p 8·8%) than patch (mean f 0·7%, p 2·0%) and plaque-stage lesions (mean f 1·1%, p 2·0%) (P < 0·05). Plk1 ranged from 0% to 18% in f and 0% to 24% in p samples. p tissue revealed a higher mean Plk1 detection rate of 4·4% compared with 2·9% in f tissue with no statistical significance.

CONCLUSIONS

Our results indicate that in CTCL, Plk1 is increased mainly in advanced lesions. Several Plk1 inhibitors have already shown promising results in preclinical and clinical phase I and II trials for different types of cancers with low adverse effects. Immunohistochemical detection of high Plk1 levels in patients with CTCL could help select individuals who might benefit from treatment with small molecule Plk1 inhibitors.

摘要

背景

丝氨酸/苏氨酸激酶 Polo 样激酶 1(Plk1)在有丝分裂过程中具有多种功能。许多癌症和血液恶性肿瘤中 Plk1 水平较高,而大多数分化组织中 Plk1 水平较低。

目的

评估 Plk1 在皮肤 T 细胞淋巴瘤(CTCL)中的免疫反应性,作为一种潜在的治疗靶点,以区分病变类型之间的 Plk1 水平,并比较新鲜冷冻(f)与石蜡包埋(p)组织中 Plk1 的检测水平。

方法

对 49 例 CTCL 患者的 65 例活检标本进行 Plk1 抗体免疫组织化学染色。46 例活检标本同时提供 f 和 p 组织进行比较。

结果

肿瘤期 CTCL 病变的 Plk1 表达(平均 f 7.7%,p 8.8%)明显高于斑片(平均 f 0.7%,p 2.0%)和斑块期病变(平均 f 1.1%,p 2.0%)(P < 0.05)。f 组织中 Plk1 范围为 0%至 18%,p 组织中 Plk1 范围为 0%至 24%。p 组织的平均 Plk1 检测率为 4.4%,明显高于 f 组织的 2.9%,但无统计学意义。

结论

我们的研究结果表明,在 CTCL 中,Plk1 主要在晚期病变中增加。几种 Plk1 抑制剂已在不同类型癌症的临床前和 I/II 期试验中显示出良好的疗效,不良反应低。CTCL 患者中 Plk1 水平升高的免疫组织化学检测可能有助于选择可能受益于小分子 Plk1 抑制剂治疗的个体。

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