Expression of p27(Kip1), cyclin D3 and Ki67 in BPH, prostate cancer and hormone-treated prostate cancer cells

Abstract

p27((Kip1)), cyclin D3 and Ki67 are the markers of DNA damage and cell proliferation. The goal of the current study was to analyze expression of the markers in benign and malignant prostate cancer tissues. Activity of p27((Kip1)), cyclin D3 and Ki67 was immunohistochemically evaluated in different cells of BPH, prostate cancer (PCa) and hormonally treated prostate cancer (HTPCa) tissues. The tissue samples were derived by means of TURP or radical prostatectomy. Intensity of the expression was compared between the groups, and association was sought with clinical parameters. Total expression of p27((Kip1)) was significantly higher in BPH as compared with PCa. Epithelial marker expression was higher in HTPCa than in PCa. Intensity of the expression in epithelial, vascular and ductal cells was negatively associated with the tumor stage and Gleason grades. Total Ki67 activity was positively correlated with patient age and serum PSA level. There was significantly higher expression in PCa and hormone-escaped PCa (HEPCa) as compared with BPH. Epithelial and vascular marker expression was positively associated with tumor stage and Gleason grades. There was a positive correlation between cyclin D3 and serum PSA level. With the increase of Gleason grades, cyclin D3 expression increased significantly. Expression of p27((Kip1)) negatively correlated with Ki67 and cyclin D3, while the latter two markers correlated positively. p27((Kip1)) is down-regulated, whereas Ki67 and cyclin D3 are up-regulated in PCa. Intensity of the markers' expression is associated with tumor stage and grades. Hormonotherapy of PCa causes activation of p27((Kip1)). HEPCa is characterized by increased Ki67 expression.

Lack of prognostic significance of p16 and p27 after radical prostatectomy in hormone-naïve prostate cancer

“…However, differences in sample size (only 30 PCs), surgical technique (80% perineal prostatectomy), immunohistochemical evaluation (whole tissue area), follow up (only 21 months) and cases of biochemical recurrence (only 7%) do not allow direct comparison between this study and ours [30]. Likewise, the reported high frequency of cytoplasmic p27 localization in high grade tumors compared to low-grade ones [31] cannot be confirmed by our results, as we performed only nuclear p27 IHC assessment, consistent with the majority of previous studies.…”

Occurrence of urolithins, gut microbiota ellagic acid metabolites and proliferation markers expression response in the human prostate gland upon consumption of walnuts and pomegranate juice

“…In an effort to investigate a potential effect in the prostate gland at the gene expression level derived from the intake of ETs‐rich food, we measured and compared the mRNA quantities of CDKN1A (p21) , MKi‐67 and c‐Myc in prostate tissues from control and supplemented patients. The pre‐selection of these cancer‐related markers was based on their key role on cell cycle and cell proliferation regulation 25, the reported differential expression of these genes in BPH and in PCa 27, 28, 33–36 and the modulation of their expression in PCa cells after exposure to PE 13, 30. In agreement with the previous reports 26, 35, our results show a statistically significant increase in the expression of c‐Myc in the PCa samples over the BPH group.…”

“…The v‐myc myelocytomatosis viral oncogene homolog (avian) ( c‐Myc ) is a strong positive regulator of cell proliferation and has been found to be amplified in up to 72% of androgen‐independent PCa 26. MKi‐67 or antigen identified by monoclonal antibody Ki‐67 is a marker of cell growth and proliferation whose expression is increased in PCa and BPH relative to normal tissue 27, 28. Since the abnormal expression of these molecules is involved in cancer development and progression, the characterization of the proliferation patterns of BPH and PCa by analyzing the expression of genes involved in the regulation of cell cycle and proliferation may yield important information on the cells response to new therapeutic drugs and treatments.…”

The AR dependent cell cycle: Mechanisms and cancer relevance

“…With few exceptions, clear and diverse clinical correlates are associated with alterations of p27 kip1 (Ben-Izhak et al, 2003; Chang et al, 2004; Cheng et al, 2000; Cheville et al, 1998; Claudio et al, 2002; Cordon-Cardo et al, 1998; Cote et al, 1998; De Marzo et al, 1998; Doganavsargil et al, 2006; Dreher et al, 2004; Drobnjak et al, 2003; Erdamar et al, 1999; Fernandez et al, 1999; Freedland et al, 2003; Guo et al, 1997; Halvorsen et al, 2003; Huang et al, 2008; Kibel et al, 2001, 2000, 2003; Kuczyk et al, 1999, 2001; Li et al, 2006; Nguyen et al, 2009; Nikoleishvili et al, 2008; Ribal et al, 2003; Romics et al, 2008; Thomas et al, 2000; Tsihlias et al, 1998; Vis et al, 2000, 2002; Wolters et al, 2010; Wu et al, 2007; Yang et al, 2002, 1998; Zeng et al, 2004) versus p21 cip1 (Aaltomaa et al, 1999; Baretton et al, 1999; Cheng et al, 2000; Facher et al, 1997; Lacombe et al, 2001; Matsushima et al, 1998; Omar et al, 2001; Sarkar et al, 1999). As detailed in Supplementary Table 1, low or no p27 kip1 is generally associated with poor outcomes, including shorter time to biochemical recurrence and reduced survival.…”