Reduction of PTEN and p27kip1 expression correlates with tumor grade in prostate cancer. Analysis in radical prostatectomy specimens and needle biopsies

Abstract

The extreme variability of prostate cancer implies latent disease with missing clinical symptoms in some cases. Tumor suppressors PTEN (phosphatase and tensin homolog deleted on chromosome ten) and p27kip1 are frequently mutated in various human cancers. PTEN negatively influences cell growth and induces apoptosis, while p27kip1 binds to cyclin-E-Cdk2 and counteracts mitosis. This study investigated the expression of PTEN and p27kip1 in prostatectomies and needle biopsies in order to determine whether protein localization or expression levels are correlated with tumor grade and whether PTEN and p27kip1 expression in biopsies are valuable predictive tumor markers. Analysis of PTEN demonstrated that weak expression levels were significantly more prevalent in high-grade tumors. Analysis of p27kip1 revealed that high-grade tumors had a higher percentage of cytoplasmic localization of the protein than low-grade tumors, where nuclear localization was more frequent. Furthermore, this study indicated a positive association between PTEN and p27kip1 levels. An increase of high-grade tumors corresponded to a progressive loss of both tumor suppressors in needle biopsies and prostatectomies. p27kip1 and PTEN did not show a higher predictive accuracy of the tumor grade in the surgical specimen than the Gleason score. However, p27kip1 had the same predictive value as the Gleason score in needle biopsies.

Cancer genetics-guided discovery of serum biomarker signatures for diagnosis and prognosis of prostate cancer

“…S4), confirming previous reports (25,26). The Gleason grading available for 69 tumors and the corresponding quantitative SRM serum analysis served as the basis for applying the bioinformatics approach outlined above (Fig.…”

“…S3 A and B). Because PTEN loss is causally associated with accelerated PCa progression and aggressiveness, as exemplified by the association between PTEN loss of function and Gleason sum score (25,26), we next asked whether the bioinformatic approach also could extract serum protein signatures reflecting tumor grading. Examination of our TMA-P92 revealed a corre- , and Ceruloplasmin (CP) selected by random forests and subsequent bootstrapped exhaustive search is based on the frequency in which the candidates appear in the best 50 predicting models.…”

The nuclear affairs of PTEN

“…In pancreatic tissue, Perren and co-workers also observed nuclear PTEN in normal islet cells but predominantly cytoplasmic PTEN in sporadic endocrine pancreatic tumors (Perren et al, 2000). The loss of nuclear PTEN specifically has now been found in a variety of sporadic tumors (Brenner et al, 2002;Depowski et al, 2001;Dreher et al, 2004;Perren et al, 2000). Perhaps the first compelling evidence for a role of nuclear PTEN came from studies of melanoma.…”

PTEN and GSK3β: key regulators of progression to androgen-independent prostate cancer

“…However, as PrCa is a heterogeneous and multifocal disease, PTEN loss is not an exclusive event (Dreher et al, 2004;Koksal et al, 2004). Through immunohistochemical analysis of human PrCas, a significant portion (>60%) of advanced cases occur in the presence or with mixed expression of PTEN (McMenamin et al, 1999), but with consistently elevated PI3K/Akt signalling.…”