Quantification of the heterogeneity of cytokeratin 18 immunoexpression in prostate adenocarcinoma and normal prostate: Global and local features

Abstract

There are few studies comparing global versus local changes in spatial patterns in prostate cancer. In this study, stereological tools have been applied to find out if the cytokeratin18 (ck18) immunoexpression shows local changes in cancer compared to normal prostate. To verify if these changes are relevant to ascertain differences between normal (CTR) and cancer (Ca) cases, several parameters were estimated. Volume fraction of epithelium immunostained for ck18 (VV ck18), dispersion index of VV ck18, positional variance of VV ck18, and multiscale entropy analysis (MSE) to measure the tissue heterogeneity. The MSE values showing significant differences between CTR and Ca were employed in a discriminant analysis to determine if MSE was able to classify the cases in CTR and Ca groups. The findings obtained indicate that changes in the expression of ck18 by the cancer prostate are heterogeneous. The increase in local variability of ck18 immunoexpression can be related to the increase in heterogeneity of shape and size of the tumor acini. The asymmetry of distribution of the local values of VV ck18 along the axis of the space series may indicate the existence of anisotropy in the distribution of tumor acini. The increase in scale-dependent entropy for VV ck18 in cancer at the morphological level could be interpreted as the macroscopic expression of the same increase at the molecular level already described. The discriminant analysis shows that the dependence on the resolution for MSE values need to be taken into account to characterize the prostate cancer better