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芳香烃受体相互作用蛋白(AIP)免疫组化表达在胃切除术后患者中的预后作用。

Prognostic Role of Aryl Hydrocarbon Receptor Interacting Protein (AIP) Immunohistochemical Expression in Patients with Resected Gastric Carcinomas.

机构信息

Complutense University of Madrid, Madrid, Spain.

Hospital Clínico San Carlos, Madrid, Spain.

出版信息

Pathol Oncol Res. 2020 Oct;26(4):2641-2650. doi: 10.1007/s12253-020-00863-7. Epub 2020 Jul 9.

DOI:10.1007/s12253-020-00863-7
PMID:32648210
Abstract

Aryl hydrocarbon receptor (AHR) interacting protein (AIP) is a chaperone which binds to inactive AHR in the cell cytoplasm. AHR is best known for mediating the toxicity of halogenated aromatics, but it has also been linked to carcinogenesis and tumor progression in several tumor types. Our aims are to assess the features of AIP immunohistochemical (IHC) staining and to evaluate its possible role as a prognostic marker in gastric cancer (GC). Retrospective study of 147 cases of resected GC. Clinicopathological features were collected, tissue microarrays were constructed for AIP IHC and statistical analysis were performed. AIP staining was observed in 50.3% of tumors. All AIP-positive cases exhibited cytoplasmic or membranous staining, variably associated with nuclear co-staining. 93.2% of AIP-positive tumors showed AIP immunoreactivity in 100% of cells. Staining intensity was mild, moderate and intense in 33.8%, 13.5% and 52.7% of cases. Tumors were stratified according to AIP staining intensity into low expression (no or mild AIP immunoreactivity) and high expression (moderate or intense AIP immunoreactivity). 36.6% of our cases showed high AIP expression. High AIP expression was significantly and independently correlated to tumor progression and cancer death. Tumors with high AIP expression showed lower survival and higher progression rates. AIP expression might be useful for determining GC prognosis. More studies are needed to clarify the role of AHR pathway in GC, AIP expression and its potential use as a surrogate marker for selecting patients for AHR modulation therapy.

摘要

芳烃受体相互作用蛋白 (AIP) 是一种伴侣蛋白,可与细胞质中无活性的芳烃受体结合。芳烃受体以介导卤代芳烃的毒性而闻名,但它也与几种肿瘤类型的致癌作用和肿瘤进展有关。我们的目的是评估 AIP 免疫组织化学(IHC)染色的特征,并评估其作为胃癌(GC)预后标志物的可能作用。对 147 例接受 GC 切除的病例进行回顾性研究。收集临床病理特征,构建组织微阵列进行 AIP IHC,并进行统计分析。在 50.3%的肿瘤中观察到 AIP 染色。所有 AIP 阳性病例均表现为细胞质或膜染色,不同程度地伴有核共染色。93.2%的 AIP 阳性肿瘤在 100%的细胞中显示 AIP 免疫反应性。染色强度为轻度、中度和强阳性的比例分别为 33.8%、13.5%和 52.7%。根据 AIP 染色强度将肿瘤分为低表达(无或轻度 AIP 免疫反应性)和高表达(中度或强 AIP 免疫反应性)。我们的病例中有 36.6%表现出高 AIP 表达。高 AIP 表达与肿瘤进展和癌症死亡显著且独立相关。高 AIP 表达的肿瘤显示较低的生存率和较高的进展率。AIP 表达可能有助于确定 GC 的预后。需要进一步研究来阐明 AHR 通路在 GC 中的作用、AIP 表达及其作为选择 AHR 调节治疗患者的替代标志物的潜在用途。

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本文引用的文献

1
Aryl hydrocarbon receptor and lung cancer.芳香烃受体与肺癌。
Anticancer Res. 2013 Apr;33(4):1247-56.
2
Expression of aryl hydrocarbon receptor (AHR) and AHR-interacting protein in pituitary adenomas: pathological and clinical implications.芳烃受体(AHR)及AHR相互作用蛋白在垂体腺瘤中的表达:病理学及临床意义
Endocr Relat Cancer. 2009 Sep;16(3):1029-43. doi: 10.1677/ERC-09-0094. Epub 2009 Jun 25.
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A constitutively active dioxin/aryl hydrocarbon receptor induces stomach tumors.一种组成型激活的二噁英/芳烃受体可诱发胃肿瘤。
Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9990-5. doi: 10.1073/pnas.152706299. Epub 2002 Jul 9.