Value of tissue markers p27<sup>kip1</sup>, MIB‐1, and CD44s for the pre‐operative prediction of tumour features in screen‐detected prostate cancer

Vis, André N.; Rhijn, Bas W.G. van; Noordzij, Marinus A.; Schröder, Fritz H.; Kwast, Theodorus H. van der

doi:10.1002/path.1084

Cited by 41 publications

(34 citation statements)

References 25 publications

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“…This is contradictory to most tumors, where a low p27 Kip1 is associated with poor prognosis, e.g., colorectal, epithelial, ovarian, breast, gastric, Barrett's, esophageal, non-small cell lung, and prostatic carcinomas (18 -21, 32-37). The findings are, however, consistent with previous evidence that p27 Kip1 is often expressed at relatively high levels in human cancer cell lines, which are additionally characterized by increased the expression of cyclin D1 or cyclin E (38,39). Also, high levels of p27 Kip1 are associated with poor survival in invasive cervical carcinoma (16) High proliferative activity, as defined by expression of the Ki-67 analysis (MIB-1) antibody, has been shown to correlate with reduced p27 Kip1 in lymphoid neoplasms, carcinoma of the oral cavity, and endocrine tumors, including pituitary, thyroid, and parathyroid gland hyperplasia (14, 40 -43).…”

Section: Discussionsupporting

confidence: 82%

MIB-1 (KI-67) Proliferation Index and Cyclin-Dependent Kinase Inhibitor p27Kip1 Protein Expression in Nephroblastoma

Ghanem

Kwast

Sudaryo

et al. 2004

Clinical Cancer Research

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Purpose: A number of studies have indicated that the tumor proliferation marker MIB-1 and cell cycle inhibitor p27Kip1 expression are of prognostic importance in a variety of cancers. The present study was performed to evaluate the prognostic value of these molecules in Wilms' tumors.Experimental Design: MIB-1 and p27 Kip1 expressions were investigated by the means of immunohistochemical analysis of 62 Wilms' tumor. Patients were preoperatively treated by chemotherapeutic agents and had a mean follow-up of 5.7 years.Results: MIB-1 and p27 Kip1 were expressed in normal kidney tissues and in the three main components of Wilms' tumor, i.e., the blastemal, epithelial, and stromal cells. In Wilms' tumors, the percentage of MIB-1-positive cells in the blastema ranged between 0 and 42% (mean, 9.4%) and in the epithelial component between 0 and 53% (mean, 19.9%), with a significant difference (P < 0.01). The percentage of blastemal p27Kip1 -positive cells ranged between 3 and 85% (mean, 55.1%) and for the epithelial component between 1 and 87% (mean, 59%). There was a significant inverse relationship between blastemal MIB-1 and p27Kip1 expression in Wilms' tumor. Univariate analysis showed that blastemal MIB-1 and p27Kip1 expression were indicative for clinical progression and tumor-specific survival. In a multivariate analysis, blastemal MIB-1 and p27Kip1 protein expression proved to be an independent prognostic for clinical progression besides stage. Conclusions:It was concluded that both MIB-1-based proliferative activity and p27Kip1 protein expression in the blastema have prognostic impact in Wilms' tumor.

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Section: Discussionsupporting

confidence: 82%

MIB-1 (KI-67) Proliferation Index and Cyclin-Dependent Kinase Inhibitor p27Kip1 Protein Expression in Nephroblastoma

Ghanem

Kwast

Sudaryo

et al. 2004

Clinical Cancer Research

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“…On the basis of our results, the activities of known FKHR target genes should be analyzed in prostate cancer tissues. Interestingly, members of the forkhead family modulate the transcriptional regulation of p27Kip1 (13,47,65), which has been shown to be downregulated in advanced prostate cancer (34,40,79,87). Akt-mediated phosphorylation of MDM2 promotes its translocation into the nucleus where it inhibits p53 activities.…”

Section: Discussionmentioning

confidence: 99%

Caveolin-1 Maintains Activated Akt in Prostate CancerCells through Scaffolding Domain Binding Site Interactions with andInhibition of Serine/Threonine Protein Phosphatases PP1 andPP2A

Ren

Tahir

et al. 2003

Molecular and Cellular Biology

265

230

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Previously it has been reported that caveolin-1 (cav-1) has antiapoptotic activities in prostate cancer cells and functions downstream of androgenic stimulation. In this study, we demonstrate that cav-1 overexpression significantly reduced thapsigargin (Tg)-stimulated apoptosis. Examination of the phosphatidylinositol 3-kinase (PI3-K)/Akt signaling cascade revealed higher activities of PDK1 and Akt but not PI3-K in cav-1-stimulated cells compared to control cells. We subsequently found that cav-1 interacts with and inhibits serine/threonine protein phosphatases PP1 and PP2A through scaffolding domain binding site interactions. Deletion of the cav-1 scaffolding domain significantly reduces phosphorylated Akt and cell viability compared with wild-type cav-1. Analysis of potential substrates for PP1 and PP2A revealed that cav-1-mediated inhibition of PP1 and PP2A leads to increased PDK1, Akt, and ERK1/2 activities. We demonstrate that increased Akt activities are largely responsible for cav-1-mediated cell survival using dominant-negative Akt mutants and specific inhibitors to MEK1/MEK and show that cav-1 increases the half-life of phosphorylated PDK1 and Akt after inhibition of PI3-K by LY294002. We further demonstrate that cav-1-stimulated Akt activities lead to increased phosphorylation of multiple Akt substrates, including GSK3, FKHR, and MDM2. In addition, overexpression of cav-1 significantly increases translocation of phosphorylated androgen receptor to nucleus. Our studies therefore reveal a novel mechanism of Akt activation in prostate cancer and potentially other malignancies.Prostate cancer remains the second leading cause of cancer mortality among American males. The predominant reason for such high and persistent mortality is the lack of curative therapies for androgen-resistant metastatic disease. It is critical to elucidate the molecular mechanisms that underlie the ultimate androgen-resistant state of prostate cancer and to develop effective therapies for this condition.Previously, Yang et al. reported that caveolin-1 (cav-1) levels were elevated in metastatic mouse and human prostate cancer (85). cav-1 is a major component of caveolae, flask-shaped membrane invaginations which are involved in multiple cellular processes, including the regulation and transportation of cellular cholesterol and lipids, clathrin-independent endocytosis, and signal transduction (24,27,60,62,66). The participation of cav-1 in these critical pathways involves the interaction of cav-1 with a relatively large number of molecules in either a scaffolding binding-dependent or -independent manner (41, 63). The wide spectrum of molecular interactions involving cav-1 is consistent with important, context-dependent roles for cav-1 in signal transduction, molecular transport, and other regulatory activities.The biological functions of cav-1 in cancer are complex, multifaceted, and somewhat controversial (42,55,72,73). Numerous experimental results indicate that cav-1 is a growth suppressor (14,17,35). Some investigators have assert...

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“…This might explain why MIB alone has not been a very strong preoperative prediction marker in screen-detected cancers in general. 26 However, our recent findings 14 on radical prostatectomies suggest that Ki-67 can predict clinical behavior of tumors within identical Gleason score. In the present study, a small proportion of the focal cancers was highly proliferative.…”

Section: Discussionmentioning

confidence: 99%

Biological aggressiveness of prostate cancer in the Finnish screening trial

Laurila

Tammela

Auvinen

et al. 2008

Intl Journal of Cancer

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Prostate cancer aggressiveness was evaluated based on pathologic characterization of cases detected in the Finnish prostate cancer screening trial. The trial population consists of 80,458 men aged 55-67 years. A total of 32,000 men were randomized to the screening arm. The remaining 48,000 men formed the control arm. The interval cases and cancers among nonparticipants and in the control arm were identified from the Finnish Cancer Registry. Random samples were selected from screen-detected cases (126 of 543 in the first and 133 of 508 in the second round) and control arm cancers (133 out of 863), in addition to all 92 interval cancers and 106 cases among nonparticipants. All the biopsies were regraded according to the Gleason system. The expression of the proliferation antigen Ki-67 was determined in 479 cases (72%). More than half of the tumors diagnosed in the first round of screening were high-grade cancers (Gleason 7 or higher). In the second round, the proportion of low-grade cancers increased from 47% to 70%. Cancers in the screening arm were more commonly focal and fewer bilateral cancers were detected. The cancers among nonparticipants were the most aggressive group. The aggressiveness of the interval cancers was between the cancers detected in the first and the second round. Our results indicate that prostate cancers detected through screening are less biologically aggressive. This was most notable after the first screening round. Nonparticipants had more aggressive cancers. ' 2008 Wiley-Liss, Inc.Key words: prostate neoplasms; prostate cancer; screening; prostatespecific antigen; proliferation antigen Prostate cancer is the most commonly diagnosed noncutaneous cancer in men in the Western world and is the second most frequent cause of cancer-related deaths in men.1 More than 95% of malignant prostate neoplasms are adenocarcinomas, and in general, the term prostate cancer is used to designate primary adenocarcinoma. However, prostate cancer comprises a wide spectrum of biological and clinical behavior, ranging from a minute latent tumor to a highly aggressive, life-threatening disease.2 Today, majority of prostate cancers are detected based on serum prostatespecific antigen (PSA). The ultimate goal of prostate cancer screening is to reduce the disease-specific mortality. However, because the biological behavior and the natural course of prostate cancer and its relation to PSA is not known, controlled randomized screening studies are needed to evaluate the effects of early detection and treatment of cancer in mortality and in quality of life.3 The European Randomized Study of Screening for Prostate Cancer (ERSPC) is a multicenter, randomized trial, which started in 1994. 4 Within the ERSPC, approximately 193,000 men from 8 European countries have been randomized, of whom approximately 40% are from Finland with a sample size of approximately 80,000 men. ) is a protein that recognizes nuclear antigens in the cell cycle from the late G1 phase, in S and G2 phases to M phase but not in noncycling cells in G...

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Value of tissue markers p27^kip1, MIB‐1, and CD44s for the pre‐operative prediction of tumour features in screen‐detected prostate cancer

Cited by 41 publications

References 25 publications

MIB-1 (KI-67) Proliferation Index and Cyclin-Dependent Kinase Inhibitor p27Kip1 Protein Expression in Nephroblastoma

MIB-1 (KI-67) Proliferation Index and Cyclin-Dependent Kinase Inhibitor p27Kip1 Protein Expression in Nephroblastoma

Caveolin-1 Maintains Activated Akt in Prostate CancerCells through Scaffolding Domain Binding Site Interactions with andInhibition of Serine/Threonine Protein Phosphatases PP1 andPP2A

Biological aggressiveness of prostate cancer in the Finnish screening trial

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Value of tissue markers p27kip1, MIB‐1, and CD44s for the pre‐operative prediction of tumour features in screen‐detected prostate cancer

Cited by 41 publications

References 25 publications

MIB-1 (KI-67) Proliferation Index and Cyclin-Dependent Kinase Inhibitor p27Kip1 Protein Expression in Nephroblastoma

MIB-1 (KI-67) Proliferation Index and Cyclin-Dependent Kinase Inhibitor p27Kip1 Protein Expression in Nephroblastoma

Caveolin-1 Maintains Activated Akt in Prostate CancerCells through Scaffolding Domain Binding Site Interactions with andInhibition of Serine/Threonine Protein Phosphatases PP1 andPP2A

Biological aggressiveness of prostate cancer in the Finnish screening trial

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Value of tissue markers p27^kip1, MIB‐1, and CD44s for the pre‐operative prediction of tumour features in screen‐detected prostate cancer