Racial Differences in 3-D Nuclear Chromatin Patterns of Prostate Cancer

Abstract

Purpose: There is a significant difference in prostate cancer incidence and stage corrected mortality between African-American (AA) and Caucasian-American (CA) men. These differences have largely been contributed to social- economic factors, yet variation in prostate cancer related gene expression has been found as well. The aim of this study was to analyze whether these differences are reflected also in the 3-D distribution patterns of the nuclear chromatin. Materials and Methods: Prostatectomy sections from 21 prostate cancer patients (10 AA and 11 CA) were cut and nuclear DNA was stained with TO-PRO-3. 3-D image stacks of selected malignant areas were obtained by confocal laser scan- ning microscopy. Image analysis was performed using in-house developed software for 3-D semi-automated segmentation and computation of DNA content and our previously developed 3-D nuclear texture features. The power of these features to discriminate between AA and CA patients was established by univariate ROC and linear discriminant analyses, stratify- ing for prognosis. Results: Five 3-D texture features discriminated between AA and CA men irrespective of prognosis, 27 features had dis- criminative value for AA and CA men in the subgroup of bad prognosis patients, and 8 features in the good prognosis subgroup. Several features had additional discriminative value in multivariate discriminant analysis. Conclusions: There are differences in the 3-D nuclear chromatin distribution between AA and CA men with similar prog- nosis. This is further evidence that the differences of prostate cancer in AA and CA men are not only related to socioeco- nomic differences, but also to genomic differences.