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

Urology. 2006 Oct;68(4):898-904. doi: 10.1016/j.urology.2006.05.008.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian
  • Asian People
  • Biomarkers, Tumor / analysis
  • Cell Nucleus / pathology*
  • Enzyme Precursors / analysis
  • Enzyme Precursors / biosynthesis
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Male
  • Pilot Projects
  • Prostate-Specific Antigen / analysis
  • Prostate-Specific Antigen / biosynthesis*
  • Prostatectomy
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / ethnology*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / surgery
  • Retrospective Studies

Substances

  • Biomarkers, Tumor
  • Enzyme Precursors
  • Prostate-Specific Antigen