Computer-assisted image analysis-derived intermediate endpoints

Cw. Boone et al., Computer-assisted image analysis-derived intermediate endpoints, UROLOGY, 57(4A), 2001, pp. 129-131
Citations number
Categorie Soggetti
Urology & Nephrology
Journal title
ISSN journal
0090-4295 → ACNP
Year of publication
129 - 131
SICI code
The development of prostatic lesions undergoes a slow progression. To estab lish efficacy of chemopreventive intervention it is therefore necessary to define surrogate endpoint biomarkers. Such biomarkers should be sensitive i n their ability to indicate response. They should be objective, ie, the res ult of measurement, and numerically defined so that a statistical validatio n 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 secret ory and luminal cells in prostatic intraepithelial neoplastic lesions has b een shown to be well defined. It can be represented by a set of features. T hese have been used to define a progression curve along which progression o r regression of a lesion can be assessed. One could define a fixed endpoint , or one might choose to accept a statistically significant regression alon g the progression curve as criterion for chemopreventive efficacy. Expected difficulties could arise from lesion heterogeneity, as it would af fect the sampling, and from multifocal lesions of differing progressions. L esion heterogeneity thus limits the precision with which regression could b e detected. These problems might be partially overcome by observations taken in histolo gically normal appearing regions of the prostate. The nuclear chromatin pat tern of secretory cell nuclei measured in such tissue regions from prostate s harboring intraepithelial or malignant lesions has been shown to exhibit distinctive changes from the chromatin pattern seen in secretory cell nucle i from prostates free from any such lesions. These changes appear to be exp ressed in the tissue up to a substantial distance from a lesion. The expres sion of changes in the nuclear chromatin suggests the existence of an intra epithelial preneoplastic lesion that can be detected by biomarkers, but whi ch is not apparent from visual microscopic inspection. Since chemoprevention might be expected to be most effective at the earlies t stages of lesion development, the assessment of such early alterations is seen as highly relevant to efforts to validate the efficacy of chemopreven tive intervention. (C) 2001, Elsevier Science Inc.