Ki-67 and outcome in clinically localised prostate cancer: analysis of conservatively treated prostate cancer patients from the Trans-Atlantic Prostate Group study

Berney, Daniel M.; Gopalan, Anuradha; Kudahetti, Sakunthala C.; Fisher, Gabrielle; Ambroisine, Laurence; Foster, Christopher S.; Reuter, Victor E.; Eastham, James A.; Møller, Henrik; Kattan, Michael W.; Gerald, William L.; Cooper, Christopher S.; Scardino, Peter T.; Cuzick, Jack

doi:10.1038/sj.bjc.6604951

Cited by 110 publications

(114 citation statements)

References 25 publications

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“…When Hsp-27 dissociates from the complex before Akt activation, apoptosis is induced. In androgenindependent prostate cancer, lethal progression is associated with reduced apoptosis (Berges et al, 1995) and enhanced tumour cell proliferation (McLoughlin et al, 1993;Berney et al, 2009 (Landry et al, 1992). However, this process appears to be promiscuous in cancer cells, being dependent on the particular kinase activation pathway invoked and the individual cell system involved.…”

Section: Discussionmentioning

confidence: 99%

Hsp-27 expression at diagnosis predicts poor clinical outcome in prostate cancer independent of ETS-gene rearrangement

et al. 2009

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Background: This study was performed to test the hypothesis that expression of small heat shock protein Hsp-27 is, at diagnosis, a reliable predictive biomarker of clinically aggressive prostate cancer. Methods: A panel of tissue microarrays constructed from a well-characterised cohort of 553 men with conservatively managed prostate cancer was stained immunohistochemically to detect Hsp-27 protein. Hsp-27 expression was compared with a series of pathological and clinical parameters, including outcome. Results: Hsp-27 staining was indicative of higher Gleason score ( P <0.001). In tissue cores having a Gleason score >7, the presence of Hsp-27 retained its power to independently predict poor clinical outcome ( P <0.002). Higher levels of Hsp-27 staining were almost entirely restricted to cancers lacking ERG rearrangements ( χ 2 trend=31.4, P <0.001), although this distribution did not have prognostic significance. Interpretation: This study has confirmed that, in prostate cancers managed conservatively over a period of more than 15 years, expression of Hsp-27 is an accurate and independent predictive biomarker of aggressive disease with poor clinical outcome ( P <0.001). These findings suggest that apoptotic and cell-migration pathways modulated by Hsp-27 may contain targets susceptible to the development of biologically appropriate chemotherapeutic agents that are likely to prove effective in treating aggressive prostate cancers.

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Section: Discussionmentioning

confidence: 99%

Hsp-27 expression at diagnosis predicts poor clinical outcome in prostate cancer independent of ETS-gene rearrangement

et al. 2009

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“…However, Ki-67 expression did not discriminate the BRCA-associated cancers as an independent cohort. In a number of different studies, Ki-67 expression predicts prognosis and clinical progression in breast (15,25) and prostate cancers (6,8,26). Although the precise biological function of Ki-67 protein is not understood, Ki-67 protein expression is an informative prognostic biomarker in the majority of malignant diseases (27).…”

Section: Discussionmentioning

confidence: 99%

“…Hitherto, the molecular genetic basis of the aggressive phenotype promoted by BRCA1 and BRCA2 mutations has not been elucidated. However, in sporadic prostate cancers, elevated cell proliferation identified by increased expression of Ki-67 protein is associated with a more malignant phenotype and higher Gleason grade (6)(7)(8). Morphologically, there is no pathognomonic feature that distinguishes BRCA mutation-related prostate cancers (9).…”

Section: Introductionmentioning

confidence: 99%

“…Using the MIB-1 antibody to detect Ki-67 protein in histopathological tissues, we have previously analysed the relationship between tumour cell proliferation and the behaviour of individual prostate cancers (6)(7)(8). Other studies have investigated the expression of Ki-67 in a variety of malignancies and have confirmed a relationship with tumour aggression.…”

Section: Introductionmentioning

confidence: 99%

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Elevated expression of Ki-67 identifies aggressive prostate cancers but does not distinguish BRCA1 or BRCA2 mutation carriers

Mitra

Jameson²,

Barbáchano³

et al. 2009

Oncol Rep

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Abstract. Prostate cancers in men with germline BRCA1 and BRCA2 mutations are more aggressive than morphologically similar cancers in men without these mutations. This study was performed to test the hypothesis that enhanced expression of Ki-67, as a surrogate of cell proliferation, is a characteristic feature of prostate cancers occurring in BRCA1 or BRCA2 mutation carriers. The study cohort comprised 20 cases of prostate cancer in mutation carriers and 126 control sporadic prostate cancers. Of the combined sample cohort, 65.7% stained only within malignant tissues while 0.7% stained in both malignant and benign tissues (p<0.001). Significantly increased expression of Ki-67 occurred in prostate cancers with higher Gleason score (p<0.001). Elevated Ki-67 expression was identified in 71% of prostate cancers in BRCA1 or BRCA2 mutation carriers and in 67% of the sporadic controls (p>0.5). Similar results were obtained when the data were analysed using a threshold set at 3.5 and 7.1%. This study shows that elevated expression of Ki-67 is associated both with aggressive prostate cancers and with high Gleason score irrespective of whether their occurrence is against a background of BRCA1 or BRCA2 mutations or as sporadic disease. The data suggest that, since elevated Ki-67 does not distinguish prostate cancers occurring in BRCA1 or BRCA2 mutation carriers from sporadic prostatic malignancies, the effects of these genetic mutations are probably independent. While all prostate cancers occurring in the presence of BRCA germline mutations are clinically aggressive, their potentially different phenotypes consistently involve maximal rates of cell proliferation.

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“…Ki-67 is a monoclonal antibody developed against a nuclear antigen only available in proliferated cells. Determining Ki-67 expression levels has been demonstrated to be helpful in predicting the prognosis of breast cancer, prostate cancer and many other malignancies such as malign mesothelioma [12,13,14].…”

Section: Introductionmentioning

confidence: 99%

Comparison of SKIP expression in malignant pleural mesotheliomas with Ki-67 proliferation index and prognostic parameters

Türkçü

Alabalık²,

Keleş³

et al. 2016

pjp

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We aimed to determine the presence of SKI-interacting protein (SKIP) expression in malignant pleural mesothelioma (MPM) and its effect on prognosis by investigating SKIP correlation with the Ki-67 proliferation index and prognostic parameters. Pathological preparations of the patients diagnosed with MPM between 2006 and 2012 were evaluated. Immunohistochemical analyses were performed to evaluate the expression of SKIP and the Ki-67 proliferation index. Correlations between SKIP expression, clinicopathological factors and survival were investigated. Survival data were calculated using the Kaplan-Meier method, and Cox regression analysis was used to evaluate the prognostic value of the variables. In total, 52 patients were evaluated in the study; 36 of them were male and 16 were female. The mean age of the patients was 62.3 ±12.2 years. The median overall survival period was 8.5 months. Factors negatively affecting general survival in the univariate analysis included high SKIP expression, Ki-67 proliferative index over 30%, presence of non-epithelioid type MPM and stage III-IV disease (p < 0.05). Cox regression analysis revealed that high SKIP expression, high Ki-67 proliferative index and presence of non-epithelioid type MPM are independent factors that affect the survival rate. Higher SKIP expression is associated with poor prognosis in MPM.

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Ki-67 and outcome in clinically localised prostate cancer: analysis of conservatively treated prostate cancer patients from the Trans-Atlantic Prostate Group study

Cited by 110 publications

References 25 publications

Hsp-27 expression at diagnosis predicts poor clinical outcome in prostate cancer independent of ETS-gene rearrangement

Hsp-27 expression at diagnosis predicts poor clinical outcome in prostate cancer independent of ETS-gene rearrangement

Elevated expression of Ki-67 identifies aggressive prostate cancers but does not distinguish BRCA1 or BRCA2 mutation carriers

Comparison of SKIP expression in malignant pleural mesotheliomas with Ki-67 proliferation index and prognostic parameters

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