Prognostic significance of proliferation activity and neuroendocrine differentiation to predict treatment failure after radical prostatectomy

May, Matthias; Siegsmund, M.; Hammermann, Fränze; Loy, V.; Gunia, Sven

doi:10.1080/00365590701224445

Cited by 36 publications

(33 citation statements)

References 26 publications

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“…Herein, we showed that all the markers in our study are mutually and strongly associated (Tables 2 and 3). T h e w e l l -d o c u m e n t e d c o r r e l a t i o n s (18,23,25,26) between the Ki-67 expression and the aggressive features of PCa were confirmed here by the demonstration of its significant association with Gleason score, ChrA expression and survival. On the other hand, the absence of correlation with the NeuroD1 and AR (Figure-2) could be explained by the fact that Ki-67 is only a marker of proliferation, whereas NeuroD1 and AR are implicated into the neuroendocrine differentiation pathway (9,14,27,28).…”

Section: Commentssupporting

confidence: 60%

“…The NED (mainly identified by tissue ChrA positive staining) seems to be useful as predictor for biochemical failure after radical prostatectomy in clinically localized PCa (21)(22)(23) and in low Gleason score PCa (23). As far as NE activity is concerned it will be difficult to detect as the knowledge of NED pathophysiology remains obscure, prompting the search for new biomarkers (14).…”

Section: Commentsmentioning

confidence: 99%

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Parallel determination of NeuroD1, Chromogranin-A, KI67 and androgen receptor expression in surgically treated prostate cancers

Cindolo¹,

Cantile

Franco

et al. 2011

Int. braz j urol.

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Purpose: Neuroendocrine differentiation is a hallmark of prostate cancer. The aim of our study was the detection of the parallel expression of neuroendocrine related markers using a prostate tissue microarray (TMA). Materials and Methods: Our study was aimed at detecting the parallel expression of NeuroD1, Chromogranin-A (ChrA), Androgen Receptor (AR) and Ki-67 by immunohistochemistry on prostate cancer tissue microarray. The data was analyzed using SAS version 8.2 (SAS Inc, Cary, NC). The relationships between NeuroD1, ChrA and AR expressions and patients' characteristics were investigated by multivariate logistic regression analysis. Progression and Overall Survival (OS) distributions were calculated using Kaplan-Meier method. Results: Tissue reactivity for NeuroD1, ChrA and AR concerned 73%, 49% and 77% of the available cases, respectively. Regarding overall survival, there were 87 deaths and 295 patients alive/censored (6 years of median follow-up). Seventyseven disease progressions occurred at the median follow-up 5.4y. A significant correlation between NeuroD1, ChrA and AR expression was observed (p < 0.001 and p < 0.03, respectively). Additionally, ChrA was strongly associated in multivariate analysis to Gleason score and Ki67 expression (p < 0.009 and p < 0.0052, respectively). Survival analysis showed no association between markers neither for overall nor for cancer-specific survival. Conclusions:The results highlight that NeuroD1, Chromogranin-A and Androgen Receptor are strongly associated, however their expression does not correlate with overall survival or disease progression.

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Section: Commentssupporting

confidence: 60%

Section: Commentsmentioning

confidence: 99%

Parallel determination of NeuroD1, Chromogranin-A, KI67 and androgen receptor expression in surgically treated prostate cancers

Cindolo¹,

Cantile

Franco

et al. 2011

Int. braz j urol.

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“…High Gleason score, and also advanced local stage, have been associated with high cancer cell proliferation index in several published studies (Vesalainen et al , 1995; May et al , 2007; Fleischmann et al , 2012; Lopez-Beltran et al , 2012). This has been also confirmed in the current study, where a fraction of about 25% of tumours treated either with radiotherapy or with surgery showed 10–20% of cancer cells undergoing active cell cycle and, indeed, such tumours were frequently of high Gleason score and expressed extraprostatic involvement.…”

Section: Discussionmentioning

confidence: 96%

Lactate dehydrogenase 5 isoenzyme overexpression defines resistance of prostate cancer to radiotherapy

et al. 2014

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Background:Radiotherapy provides high-cure rates in prostate cancer. Despite its overall slow clinical growth, high proliferation rates documented in a subset of tumours relate to poor radiotherapy outcome. This study examines the role of anaerobic metabolism in prostate cancer growth and resistance to radiotherapy.Methods:Biopsy samples from 83 patients with prostate cancer undergoing radical hypofractionated and accelerated radiotherapy were analysed for MIB1 proliferation index and for lactate dehydrogenase isoenzyme LDH5, a marker of tumour anaerobic metabolism. Ninety-five surgical samples were in parallel analysed. Correlation with histopathological variables, PSA and radiotherapy outcome was assessed. Dose–response experiments were performed in PC3 and DU145 cancer cell lines.Results:High MIB1 index (noted in 25% of cases) was directly related to Gleason score (P<0.0001), T3-stage (P=0.0008) and PSA levels (P=0.03). High LDH5 (noted in 65% of cases) was directly related to MIB1 index (P<0.0001), Gleason score (P=0.02) and T3-stage (P=0.001). High Gleason score, MIB1, LDH5 and PSA levels were significantly related to poor BRFS (P=0.007, 0.01, 0.03 and 0.01, respectively). High Gleason score (P=0.04), LDH5 (P=0.01) and PSA levels (P=0.003) were significantly related to local recurrence. MIB1 and T-stage did not affect local control. Silencing of LDHA gene in both prostate cancer cell lines resulted in significant radiosensitisation.Conclusions:LDH5 overexpression is significantly linked to highly proliferating prostate carcinomas and with biochemical failure and local relapse following radiotherapy. Hypoxia and LDHA targeting agents may prove useful to overcome radioresistance in a subgroup of prostate carcinomas with anaerobic metabolic predilection.

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“…An increased number of neuroendocrine cells have been reported in advanced tumour stages, high-grade versus low-grade tumours, and especially after patients were treated with androgen suppression (29)(30)(31). In contrast, other researchers found no correlation (61).…”

Section: -2006 13 (118%)mentioning

confidence: 71%

“…The role of immunohistochemical markers in distinguishing different subtypes of PCa is a less explored area. Some reports indicate that neuroendocrine differentiation (NED) in the tumour is a significant prognostic parameter associated with shortened survival after endocrine therapy (29)(30)(31). A number of studies have analysed Ki67, p53, or bcl-2 expression in PCa, mostly in the context of prognosis (32)(33)(34).…”

mentioning

confidence: 99%

Diagnostic problems and prognostic factors in prostate cancer

Tarján

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Prognostic significance of proliferation activity and neuroendocrine differentiation to predict treatment failure after radical prostatectomy

Abstract: Our results identify Ki-67 LI and NED as additional prognostic markers after radical prostatectomy.

Cited by 36 publications

References 26 publications

Parallel determination of NeuroD1, Chromogranin-A, KI67 and androgen receptor expression in surgically treated prostate cancers

Parallel determination of NeuroD1, Chromogranin-A, KI67 and androgen receptor expression in surgically treated prostate cancers

Lactate dehydrogenase 5 isoenzyme overexpression defines resistance of prostate cancer to radiotherapy

Diagnostic problems and prognostic factors in prostate cancer

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