Breast carcinoma, intratumour heterogeneity and histological grading, using geostatistics

Tumour progression is currently believed to result from genetic instability . Chromosomal patterns specific of a type of cancer are frequent even thoug h phenotypic spatial heterogeneity is omnipresent. The latter is the usual cause of histological grading imprecision, a well documented problem, witho ut any fully satisfactory solution up to now. The present article addresses this problem in breast carcinoma. The assessment of a genetic marker for h uman tumours requires quantifiable measures of intratumoral heterogeneity. If any invariance paradigm representing a stochastic or geostatistic functi on could be discovered, this might help in solving the grading problem. A n ovel methodological approach using geostatistics to measure heterogeneity i s used. Twenty tumours from the three usual (Scarff-Bloom and Richardson) g rades were obtained and paraffin sections stained by MIB-1 (Ki-67) and pero xidase staining. Whole two-dimensional sections were sampled. Morphometric grids of variable sizes allowed a simple and fast recording of positions of epithelial nuclei, marked or not by MIB-1. The geostatistical method is ba sed here upon the asymptotic behaviour of dispersion variance. Measure of a symptotic exponent of dispersion variance shows an increase from grade 1 to grade 3. Preliminary results are encouraging: grades 1 and 3 on one hand a nd 2 and 3 on the other hand are totally separated. The final proof of an i mproved grading using this measure will of course require a confrontation w ith the results of survival studies.