Alterations in nuclear structure and expression of proPSA predict differences between native Japanese and Japanese-American prostate cancer

Objectives: To differentiate the benign and/or malignant epithelial cells in prostate cancer (PCa) glands of native Japanese (NJ) and Japanese-American (JA) men using biomarkers. Methods: Tissue microarrays from radical prostatectomy specimens of cancerous and adjacent benign areas from 25 NJ and 25 JA prostate glands were studied. Image analysis was used to quantify total prostate-specific antigen (PSA) and proPSA immunohistochemical staining, as well as the variance of several morphometric features from Feulgen-stained epithelial cell nuclei. Logistic regression analysis was applied to determine whether quantitative nuclear grade (QNG) calculations and PSA immunohistochemical staining could differentiate the two test groups. Results: The QNG model differentiated changes in the benign epithelium of the two Japanese groups with an area under the receiver operating characteristic curve of 84% and accuracy of 82% (P = 0.0001). A second QNG model differentiated changes in the malignant epithelium of the two groups with an area under the receiver operating characteristic curve of 84% and accuracy of 76% (P = 0.0023). Logistic regression models combining proPSA immunohistochemical data and QNG from either benign or malignant tissue components yielded areas under the receiver operating characteristic curve of 96% and 91% (P <0.0001) for differentiation of the JA and NJ groups, respectively. Conclusions: Unique nuclear morphometric alterations demonstrated by QNG combined with proPSA immunohistologic localization independently predicted for significant differences between NJ and JA men with PCa. These preliminary observations indicate a basis for biologic and molecular alterations in the benign adjacent and malignant epithelium between these two groups.