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Expression of activator protein 2 in prostate cancer is related to tumor differentiation and cell proliferation
P Lipponen1, S Aaltomaa, J Kellokoski
1Department of Pathology and Forensic Medicine, University of Kuopio, Kuopio, Finland. pertti.lipponen@kuopio.fi
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-2alpha 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-2alpha 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-2alpha 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.
Insights
Activator protein 2 (AP-2) expression in prostate cancer is often cytoplasmic and reduced in poorly differentiated tumors. While nuclear AP-2 correlates with aggressive features, it ultimately shows no independent prognostic value for patient survival.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Activator protein 2 (AP-2) is a transcription factor involved in cell cycle regulation.
- AP-2 can activate p21 (waf1/cip1) expression, leading to cell growth arrest.
- Understanding AP-2 expression in prostate cancer is crucial for identifying potential prognostic markers.
Purpose of the Study:
- To investigate the expression patterns of AP-2alpha in prostate cancer tissues.
- To correlate AP-2alpha expression with established prognostic factors.
- To evaluate the prognostic significance of AP-2alpha in relation to patient survival.
Main Methods:
- Immunohistochemistry was used to detect AP-2alpha expression in 215 prostate cancer cases.
- Results were analyzed in relation to prognostic factors such as Gleason score, T category, and DNA ploidy.
- Statistical analysis, including multivariate analysis, was performed to assess prognostic value.
Main Results:
- AP-2alpha expression was predominantly weak and cytoplasmic, similar to normal prostate epithelium.
- Nuclear AP-2 expression was observed in 22% of cases and associated with high Gleason score, advanced T category, DNA aneuploidy, and high S-phase fraction.
- Low AP-2 expression correlated with high mitotic index, Ki67 labeling, and high p21 expression.
Conclusions:
- Cytoplasmic AP-2alpha expression is diminished in poorly differentiated prostate carcinomas.
- Nuclear AP-2 expression is rare and linked to aggressive tumor characteristics but lacks independent prognostic value.
- AP-2 expression does not appear to be a reliable prognostic indicator in prostate cancer.