Jw. Bacus et al., Image morphometric nuclear grading of intraepithelial neoplastic lesions with applications to cancer chemoprevention trials, CANC EPID B, 8(12), 1999, pp. 1087-1094
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.