Computer-assisted image analysis-derived intermediate endpoints
Computer-assisted image analysis-derived intermediate endpoints
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DOI：
10.1016/s0090-4295(00)00956-0
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发表时间：
2001-04-01
期刊：
影响因子：
2.1
通讯作者：
Bartels, P
中科院分区：
文献类型：
--
作者：
Boone, CW;Lieberman, R;Bartels, P
前列腺病变的发展过程缓慢。因此，为了确定化学预防干预的功效，有必要定义替代终点生物标志物。此类生物标志物指示反应的能力应该是敏感的。它们应该是客观的，即测量结果，并以数字方式定义，以便可以对响应进行统计验证。它们不仅能够指示病变进展的停止，而且能够指示进展的逆转。前列腺上皮内肿瘤病变的分泌细胞和管腔细胞中核染色质的空间和统计分布已被证明是明确的。它可以用一组特征来表示。这些已被用来定义进展曲线，沿着该曲线可以评估病变的进展或消退。人们可以定义一个固定的终点，或者可以选择接受沿着进展曲线的统计显着回归作为化学预防功效的标准。预期的困难可能来自病变异质性，因为它会影响采样，以及不同进展的多灶性病变。因此，病变异质性限制了检测退化的精确度。通过在前列腺组织学上正常的区域进行观察，可以部分克服这些问题。在来自含有上皮内或恶性病变的前列腺的此类组织区域中测量的分泌细胞核的核染色质模式已显示出与来自没有任何此类病变的前列腺的分泌细胞核中观察到的染色质模式的独特变化。这些变化似乎在距病变较远的组织中表达。核染色质变化的表达表明存在上皮内癌前病变，可以通过生物标志物检测到，但通过目视显微镜检查并不明显。由于预计化学预防可能在病变发展的最早阶段最有效，因此对此类早期改变的评估被认为与验证化学预防干预效果的努力高度相关。 (C) 2001，爱思唯尔科学公司。
The development of prostatic lesions undergoes a slow progression. To establish efficacy of chemopreventive intervention it is therefore necessary to define surrogate endpoint biomarkers. Such biomarkers should be sensitive in their ability to indicate response. They should be objective, ie, the result of measurement, and numerically defined so that a statistical validation of response is possible. They should be able to indicate not only a halt of progression of a lesion, but also a reversal of progression.The spatial and statistical distribution of nuclear chromatin in the secretory and luminal cells in prostatic intraepithelial neoplastic lesions has been shown to be well defined. It can be represented by a set of features. These have been used to define a progression curve along which progression or regression of a lesion can be assessed. One could define a fixed endpoint, or one might choose to accept a statistically significant regression along the progression curve as criterion for chemopreventive efficacy.Expected difficulties could arise from lesion heterogeneity, as it would affect the sampling, and from multifocal lesions of differing progressions. Lesion heterogeneity thus limits the precision with which regression could be detected.These problems might be partially overcome by observations taken in histologically normal appearing regions of the prostate. The nuclear chromatin pattern of secretory cell nuclei measured in such tissue regions from prostates harboring intraepithelial or malignant lesions has been shown to exhibit distinctive changes from the chromatin pattern seen in secretory cell nuclei from prostates free from any such lesions. These changes appear to be expressed in the tissue up to a substantial distance from a lesion. The expression of changes in the nuclear chromatin suggests the existence of an intraepithelial preneoplastic lesion that can be detected by biomarkers, but which is not apparent from visual microscopic inspection.Since chemoprevention might be expected to be most effective at the earliest stages of lesion development, the assessment of such early alterations is seen as highly relevant to efforts to validate the efficacy of chemopreventive intervention. (C) 2001, Elsevier Science Inc.