Assessing p53 in clinical contexts: unlearned lessons and new perspectives
Assessing p53 in clinical contexts: unlearned lessons and new perspectives
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DOI：
10.1002/path.1913
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发表时间：
2006-01-01
影响因子：
7.3
通讯作者：
McCluggage, WG
中科院分区：
文献类型：
--
作者：
Hall, PA;McCluggage, WG
有令人信服的证据表明p53通路在人类肿瘤形成中的核心作用，但尽管有大量的文献，评估这一通路的临床效用仍然模糊不清。即使是关于临床样本中p53状态评估的简单问题仍然没有答案，文献也令人困惑，而且往往相互矛盾。p53通路当然是复杂的，调节p53功能的生化机制及其下游后果是复杂的。这种观点考虑了这种复杂性，以及为什么建立p53临床评估的真正效用如此困难的原因。事实上，最近关于p53的可变剪接变体的存在、p53调控的复杂性以及p53的等位基因变体及其具有不同功能的调控物的存在的观察使得情况更加复杂。与现有的测定的问题被认为是需要考虑一系列的方法学问题被强调。较新的策略，包括分析p53下游靶点的表达和使用阈值策略来测量p53蛋白，可能会在临床环境中提供更可靠的p53途径的测量，也许再加上廉价的基于测序的突变（和多态性）检测方法。然而，只有解决这些方法学问题，并在临床试验环境中进行适当把握度研究的背景下进行稳健的测定，才能取得进展。版权所有（c）2006大不列颠和爱尔兰病理学会。出版社：John Wiley & Sons，Ltd
There is compelling evidence for the central role of the p53 pathway in human neoplasia but, despite an enormous literature, the clinical utility of assessing this pathway remains ambiguous. Even simple questions about the assessment of p53 status in clinical samples remain unanswered and the literature is confusing and often contradictory. The p53 pathway is certainly complicated and the biochemical mechanisms for regulating the function of p53 and its downstream consequences are rabbinical in complexity. This perspective considers this complexity and the reasons why establishing the true utility of clinical assessment of p53 has proven to be so difficult. Indeed, recent observations regarding the existence of alternate splice variants of p53, the complexity of p53 regulation, and the existence of allelic variants of p53 and its regulators with distinct functionality makes the situation even more complex. Problems with the available assays are considered and the need to consider an array of methodological issues is emphasized. Newer strategies including analysis of the expression of downstream targets of p53 and the use of threshold strategies to measure p53 protein may provide more robust measures of the p53 pathway in clinical settings, perhaps coupled with cheap sequencing-based approaches for mutation (and polymorphism) detection. However, progress will only be made if these methodological issues are resolved and robust assays are performed in the context of appropriately powered studies in clinical trial settings. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.