Image morphometric nuclear grading of intraepithelial neoplastic lesions with applications to cancer chemoprevention trials

A new image morphometric method of nuclear grading is described and assesse d in the context of the evaluation of histological samples from ductal carc inoma irt situ of the breast and cervical intraepithelial neoplasia, The me thod results in a continuous scaled variable, or nuclear grading scale, exp ressed in SD units from measured normal nuclei from breast or cervix. For a given histological preinvasive neoplastic lesion, the mean nuclear grade o f measured nuclei was shown to be analogous to the histopathological nuclea r grade of the same lesion assigned subjectively by the pathologist. In a c hemoprevention trial of the effect of difluoromethylornithine given for 1 m onth to subjects with cervical intraepithelial neoplasia grade 3, pathologi sts could see no difference in 14 histological sections taken before and af ter difluoromethylornithine treatment. However, the image morphometric meth od detected a systematic effect of lowered mean nuclear grade and a decreas e in the variability of nuclear grade expression. Twelve of 14 samples show ed a lower posttreatment mean nuclear grade (P < 0.05), and 13 of the 14 sa mples showed a decrease in the SD of their nuclear grade distributions (P < 0.01), This study demonstrates the use of image morphometric nuclear gradi ng in a chemoprevention setting. It may be very useful in supplementing the pathologist's histopathological grading by providing objective, quantitati ve assessments.