title: Endpoint markers for cancer chemoprevention trials derived from the lesion of precancer (intraepithelial neoplasia) measured by computer-assisted quantitative image analysis.
abstract: Endpoint markers for cancer chemoprevention clinical trials are described that are developed from the morphological properties of the precancerous lesion of intraepithelial neoplasia itself, as measured by computer-assisted quantitative image analysis. The markers include increased proliferative fraction (percentage MIB-1 positive nuclear area); nuclear DNA content (DNA ploidy), including DNA content exceeding fivefold the haploid amount (5C-exceeding rate); nuclear/nucleolar morphometry; and disorganization of nuclear chromatin pattern as characterized by Markovian parameters and other functions. A significant new advance in image analysis is the process of "tiling," in which hundreds of full monitor image fields of a given histological section at x40 magnification are reduced in size and fused seamlessly to produce a single image of the histological section at x1.25 magnification. The operator may review the low-power image and retrieve x40 magnification of any desired area by point/clicking with a mouse.
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: C W
authors.initials: CW
authors.lastname: Boone
authors.forename: G J
authors.initials: GJ
authors.lastname: Kelloff
mesh_terms: D000465:Algorithms; D002843:Chromatin / Q000648:ultrastructure; D002986:Clinical Trials as Topic; D004247:DNA / Q000032:analysis; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000295:instrumentation / Q000379:methods*; D008853:Microscopy / Q000295:instrumentation / Q000379:methods; D009369:Neoplasms / Q000517:prevention & control*; D011230:Precancerous Conditions / Q000473:pathology* / Q000628:therapy
chemical_list: D002843:Chromatin; D004247:DNA