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Determining Risk of Biochemical Recurrence in Prostate Cancer by Immunohistochemical Detection of PTEN Expression and Akt Activation
Ist Teil von
Clinical cancer research, 2007-07, Vol.13 (13), p.3860-3867
Ort / Verlag
Philadelphia, PA: American Association for Cancer Research
Erscheinungsjahr
2007
Link zum Volltext
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
Purpose: A considerable fraction of patients who undergo radical prostatectomy as treatment for primary prostate cancer experience
biochemical recurrence detected by elevated serum levels of prostate-specific antigen. In this study, we investigate whether
loss of expression of the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and the phosphorylated
form of the cell survival protein Akt (pAkt) predicts biochemical recurrence.
Experimental Design: Expression of PTEN and pAkt was detected by immunohistochemistry in paraffin-embedded prostate cancer tissue obtained from
men undergoing radical prostatectomy. Outcome was determined by 60-month follow-up determining serum prostate-specific antigen
levels.
Results: By itself, PTEN was not a good predictor of biochemical recurrence; however, in combination with pAkt, it was a better predictor
of the risk of biochemical recurrence compared with pAkt alone. Ninety percent of all cases with high pAkt and negative PTEN
were recurrent whereas 88.2% of those with low pAkt and positive PTEN were nonrecurrent. In addition, high Gleason scores
resulted in reduced protection from decreased pAkt and increased PTEN. By univariate logistic regression, pAkt alone gives
an area under the receiver-operator characteristic curve of 0.82 whereas the area under the receiver-operator characteristic
curve for the combination of PTEN, pAkt, and Gleason based on a stepwise selection model is 0.89, indicating excellent discrimination.
Conclusions: Our results indicate that loss of PTEN expression, together with increased Akt phosphorylation and Gleason score, is of significant
predictive value for determining, at the time of prostatectomy, the risk of biochemical recurrence.