Expression of Activator Protein 2 in Prostate Cancer Is Related to Tumor Differentiation and Cell Proliferation

Objectives: Activator protein 2 (AP–2) is a DNA–binding transcription factor that can activate the expression of p21 (waf1/cip1), which in turn causes growth arrest of cells through inhibition of cyclin–dependent kinases required in G1–S progression. The aims of the present study were to analyze the expression of AP–2 in prostate cancer and to relate the results of AP–2 immunohistochemistry to other known prognostic factors and patient survival.Methods: AP–2α was demonstrated by an immunohistochemical method in 215 prostate cancer cases, and the results of immunohistochemistry were related to other known prognostic factors and patient survival.Results:The expression of AP–2α in carcinomas was usually weak and cytoplasmic, similar to normal prostatic epithelium adjacent to tumors. In 6% of the tumors, the expression was strong, and in 15% no staining signal was detected. Nuclear expression was detected in 22% of cases. Low fraction of AP–2–expressing cells was related to high mitotic index, Ki67 labeling and high expression of p21 (waf1/cip1). Nuclear expression of AP–2 was related to high Gleason score, advanced T category, DNA aneuploidy and high S–phase fraction. Nuclear expression was an indicator of unfavorable disease outcome, but in multivariate analysis, expression of AP–2 had no prognostic value.Conclusions: Cytoplasmic expression of AP–2α is reduced in poorly differentiated prostate carcinomas. The rare nuclear expression occurs in a small proportion of tumors which are aneuploid, have a high T category and high Gleason score. The expression of AP–2 seems to have no prognostic value in prostate cancer.