Markers and meaning of primary treatment failure

Swindle, Peter; Kattan, Michael W.; Scardino, Peter T.

doi:10.1016/s0094-0143(02)00176-3

Cited by 75 publications

(34 citation statements)

References 133 publications

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“…The presence of this variant was significantly correlated with biochemical (PSA) recurrence following radical prostatectomy. Quantitative RT-PCR studies confirmed a significant increase in variant CDC25C mRNAs in prostate cancer and its correlation with PSA recurrence, particularly early PSA recurrence that is associated with aggressive disease and worse patient outcome (31). It should be noted that the quantitative RT-PCR assay detects other splice variants, particularly the C4 variant, which may also contribute to the observed correlation, although the C5 variant was the most highly expressed form.…”

Section: Discussionmentioning

confidence: 66%

Increased Expression and Activity of CDC25C Phosphatase and an Alternatively Spliced Variant in Prostate Cancer

Özen

Ittmann

2005

Clinical Cancer Research

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Alterations in the control of cell cycle progression have been implicated in a wide variety of malignant neoplasms, including prostate cancer. CDC25 phosphatases belong to the tyrosine phosphatase family and play a critical role in regulating cell cycle progression by dephosphorylating cyclin-dependent kinases at inhibitory residues. CDC25C plays an important role in the G 2 -M transition by activating Cdc2/Cyclin B1 complexes. To determine whether CDC25C activity is altered in prostate cancer, we have examined the expression of CDC25C and an alternatively spliced variant in human prostate cancer samples and cell lines. CDC25C protein is up-regulated in prostate cancer in comparison with normal prostate tissue and is present almost exclusively in its active dephosphorylated form. Expression of a biologically active alternatively spliced CDC25C isoform is also increased in prostate cancer and expression of alternatively spliced CDC25C is correlated to occurrence of biochemical (prostate-specific antigen) recurrence. We have also developed a quantitative reverse transcriptase-PCR analysis of Ki-67 expression as a method of measuring proliferative activity in prostate cancer from RNA samples. Based on this analysis of Ki67 expression, some but not all of this increase in CDC25C and its alternatively spliced variants is correlated with increased proliferation in prostate cancer. This data suggests that CDC25C might play an important role in prostate cancer progression and could be used to monitor and predict the aggressiveness of this disease.Abnormal expression and/or activity of cell cycle regulatory proteins have been identified in a wide variety of malignant neoplasms, including prostate cancer. Cell cycle progression is controlled by the sequential activities of cyclin-dependent kinases, whose activities are tightly regulated by cyclins, cyclin-dependent kinase inhibitors, and a variety of other proteins. Several groups have shown increased expression of cyclin B1, which plays a critical role in the G 2 -M transition, in human prostate cancers (1, 2). Recent work by Maddison et al. (3) has shown increased levels of cyclin B1 in poorly differentiated and androgen-independent prostate cancers in the TRAMP mouse model of prostate cancer. During G 2 , the Cdc2/Cyclin B complex is kept inactive by phosphorylation of Cdc2 by Wee1. At the onset of mitosis, Cdc2/Cyclin B complexes are dephosphorylated by CDC25 phosphatase leading to increased kinase activity (4 -6). Our laboratory has shown previously that disruption of fibroblast growth factor signaling in prostate cancer cells leads to decrease in Cdc2 kinase activity and arrest in G 2 followed by cell death (7). These findings imply that the G 2 -M transition may be a critical checkpoint in prostate cancer.CDC25 phosphatases belong to the tyrosine phosphatase family and play a critical role in regulating cell cycle progression by dephosphorylating cyclin-dependent kinases at inhibitory residues. In human cells, CDC25 proteins are encoded by a multigene fa...

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Section: Discussionmentioning

confidence: 66%

Increased Expression and Activity of CDC25C Phosphatase and an Alternatively Spliced Variant in Prostate Cancer

Özen

Ittmann

2005

Clinical Cancer Research

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“…Discussion There are few reliable markers for accurate prediction of prostate cancer recurrence besides preoperative PSA and Gleason sum. 48 However, nearly two thirds of patients diagnosed with prostate cancer have the preoperative PSA range 4-10 ng/ml, with T1C disease and a biopsy Gleason score of 5-7. [47][48][49][50][51][52] For such patients, one or a combination of accurate prognostic indicators could improve the physicians' ability to identify aggressive disease, so that more individualized treatments could be offered.…”

Section: Determination Of Sensitivity Specificity Accuracy Ppv Andmentioning

confidence: 99%

Cyclooxygenase‐2 (cox‐2) expression is an independent predictor of prostate cancer recurrence

Cohen

Gómez

Omori

et al. 2006

Intl Journal of Cancer

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Lack of reliable prognostic markers hinders accurate prediction of disease progression in prostate cancer. The inducible proinflammatory enzyme cyclooxygenase-2 (COX-2) is implicated in prostate carcinogenesis, but its role in cancer progression is less clear. We examined whether COX-2 expression evaluated by immunohistochemistry (IHC) in radical prostatectomy (RP) specimens can predict biochemical recurrence. Archival prostate cancer specimens (n 5 60) were obtained from patients who underwent RP, but had not received neoadjuvant hormonal therapy. Twentythree patients had biochemical or clinical recurrence (mean time of recurrence: 38.2 months), and 37 patients were recurrence free (mean follow-up: 95 months). COX-2 expression was determined by IHC, using an anti-COX-2 antibody. Three individuals scored the staining independently, as high-or low-expression. COX-2 was expressed in prostate cancer cells, in adjacent normal glands and in specimens from patients who later progressed. At 62-months follow-up, COX-2 staining predicted progression with 82.4% sensitivity and 81.3% specificity. Sensitivity (86.4%) and specificity (86.7%) improved at 100-months follow-up. In univariate analysis, Gleason score, preoperative PSA, extraprostatic extension, margin, seminal vesicle invasion, and high COX-2 expression were significant predictors of biochemical recurrence (p < 0.05). In multivariate analysis, preoperative PSA (hazard ratio/unit PSA change 1.080; p 5 0.0036) and COX-2 expression (hazard ratio 16.442; p < 0.0001) were independent prognostic indicators. Patients with PSA > 7 ng/ml and high COX-2 expression had the highest probability of recurrence (Kaplan-Meier analysis). COX-2 expression is an independent predictor of prostate cancer progression following RP and underscores the significance of inflammatory factors in this process. ' 2006 Wiley-Liss, Inc.Key words: inflammation; immunohistochemistry; PSA; cancer progression; prognostic indicators; multivariate analysis; tumor markers Cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) are prostaglandin endoperoxide synthases, which are rate limiting enzymes in the conversion of the fatty acid arachidonic acid into physiologically active eicosanoids such as prostaglandin, thromboxane and prostacyclin. 1 COX-2 is the inducible form of COX that is frequently elevated in cancer tissues. [2][3][4] Although the mechanism of COX-2 action in carcinogenesis or progression is not well established, COX-2 inhibitors have been shown to be chemopreventive in cancer, specifically in colorectal cancer. [5][6][7] The expression and role of COX-2 in prostate cancer has been a topic of several reports over the decade. 8,9 There exists some controversy over the expression, detection and the putative role of COX-2 in prostate carcinogenesis and progression. While early studies reported high-level expression of COX-2 in prostate, findings from subsequent studies have been mixed. [10][11][12] Typically, later studies reported low or no expression in normal, benign prostatic hyperplasi...

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“…It is generally accepted that PSA recurrence within 1-2 years relates to a higher risk of developing metastatic disease. 9,59 However, it is not understood whether existing pre-and postoperative parameters as well as histologic markers can distinguish between patients who will recur within 24 months and those who will not. In our study, PSA subset analysis showed that, except for margin status, none of the markers (i.e., HA, HYAL-1, HA-HYAL-1, MVD and CD44v6) and preoperative (i.e., age, clinical stage and preoperative PSA) and postoperative (i.e., Gleason sum overall or Ն7, EPE, seminal vesicle invasion) was able to distinguish between patients who recurred within 24 months and those who did not.…”

Section: Evaluation Of the Prognostic Capability Of Pre-and Postoperamentioning

confidence: 99%

Comparison of the prognostic potential of hyaluronic acid, hyaluronidase (HYAL‐1), CD44v6 and microvessel density for prostate cancer

Ekici

Cerwinka

Duncan

et al. 2004

Intl Journal of Cancer

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Despite the development of nomograms designed to evaluate a prostate cancer (PCa) patient's prognosis, the information has been limited to PSA, clinical stage, Gleason score and tumor volume estimates. We compared the prognostic potential of 4 histologic markers, hyaluronic acid (HA), HYAL-1-type hyaluronidase (HAase), CD44v6 and microvessel density (MVD) using immunohistochemistry. HA is a glycosaminoglycan that promotes tumor metastasis.

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Markers and meaning of primary treatment failure

Cited by 75 publications

References 133 publications

Increased Expression and Activity of CDC25C Phosphatase and an Alternatively Spliced Variant in Prostate Cancer

Increased Expression and Activity of CDC25C Phosphatase and an Alternatively Spliced Variant in Prostate Cancer

Cyclooxygenase‐2 (cox‐2) expression is an independent predictor of prostate cancer recurrence

Comparison of the prognostic potential of hyaluronic acid, hyaluronidase (HYAL‐1), CD44v6 and microvessel density for prostate cancer

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