Endpoint markers for cancer chemoprevention trials derived from the lesion of precancer (intraepithelial neoplasia) measured by computer-assisted quantitative image analysis.
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.
Boone
C W
CW
Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Kelloff
G J
GJ
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
D002843:Chromatin; D004247:DNA