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精确免疫检测人类肿瘤中的 PTEN 蛋白。

Precise Immunodetection of PTEN Protein in Human Neoplasia.

机构信息

Biocruces Bizkaia Health Research Institute, Barakaldo 48903, Spain.

Ikerbasque, Basque Foundation for Science, Bilbao 48011, Spain.

出版信息

Cold Spring Harb Perspect Med. 2019 Dec 2;9(12):a036293. doi: 10.1101/cshperspect.a036293.

Abstract

PTEN is a major tumor-suppressor protein whose expression and biological activity are frequently diminished in sporadic or inherited cancers. gene deletion or loss-of-function mutations favor tumor cell growth and are commonly found in clinical practice. In addition, diminished PTEN protein expression is also frequently observed in tumor samples from cancer patients in the absence of gene alterations. This makes PTEN protein levels a potential biomarker parameter in clinical oncology, which can guide therapeutic decisions. The specific detection of PTEN protein can be achieved by using highly defined anti-PTEN monoclonal antibodies (mAbs), characterized with precision in terms of sensitivity for the detection technique, specificity for PTEN binding, and constraints of epitope recognition. This is especially relevant taking into consideration that PTEN is highly targeted by mutations and posttranslational modifications, and different PTEN protein isoforms exist. The precise characterization of anti-PTEN mAb reactivity is an important step in the validation of these reagents as diagnostic and prognostic tools in clinical oncology, including their routine use in analytical immunohistochemistry (IHC). Here, we review the current status on the use of well-defined anti-PTEN mAbs for PTEN immunodetection in the clinical context and discuss their potential usefulness and limitations for a more precise cancer diagnosis and patient benefit.

摘要

PTEN 是一种主要的肿瘤抑制蛋白,其表达和生物活性经常在散发性或遗传性癌症中降低。基因缺失或功能丧失突变有利于肿瘤细胞生长,在临床实践中很常见。此外,在没有基因改变的癌症患者的肿瘤样本中,也经常观察到 PTEN 蛋白表达减少。这使得 PTEN 蛋白水平成为临床肿瘤学中潜在的生物标志物参数,可以指导治疗决策。通过使用高度定义的抗-PTEN 单克隆抗体 (mAb) 可以特异性地检测 PTEN 蛋白,这些 mAb 在检测技术的灵敏度、与 PTEN 结合的特异性以及表位识别的限制方面具有精确性。考虑到 PTEN 非常容易受到突变和翻译后修饰的靶向作用,并且存在不同的 PTEN 蛋白异构体,这一点尤其重要。精确表征抗-PTEN mAb 的反应性是将这些试剂作为临床肿瘤学中诊断和预后工具进行验证的重要步骤,包括在分析免疫组织化学 (IHC) 中常规使用这些试剂。在这里,我们回顾了在临床环境中使用定义明确的抗-PTEN mAb 进行 PTEN 免疫检测的现状,并讨论了它们在更精确的癌症诊断和患者获益方面的潜在有用性和局限性。

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