Characterisation of biomolecular profiles in primary high-grade prostate cancer treated by radical prostatectomy

Augustin, Herbert; Hammerer, Peter; Graefen, Markus; Palisaar, Jüri; Daghofer, Fedor; Huland, Hartwig; Erbersdobler, Andreas

doi:10.1007/s00432-003-0496-9

Cited by 23 publications

(18 citation statements)

References 35 publications

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“…Additionally, we evaluated a potential mechanism of Bcl‐2 overexpression on protein level. Against the background of negative regulation of p53 and Bcl‐2 expression 1 we tried to link both biomarker, but no such correlation was present what confirms findings from large sections 15–17.…”

Section: Discussionmentioning

confidence: 69%

Prognostic relevance of Bcl‐2 overexpression in surgically treated prostate cancer is not caused by increased copy number or translocation of the gene

Fleischmann¹,

Huland²,

Mirlacher³

et al. 2011

The Prostate

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Section: Discussionmentioning

confidence: 69%

Prognostic relevance of Bcl‐2 overexpression in surgically treated prostate cancer is not caused by increased copy number or translocation of the gene

Fleischmann¹,

Huland²,

Mirlacher³

et al. 2011

The Prostate

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“…Indeed, there seems to be a clear stratification between predominantly Gleason 3 pattern tumours and those containing Gleason 4 morphology [16]. This change in morphology in the Gleason 4 pattern is undoubtedly a visual clue towards the myriad of genetic and protein changes which allow these cells to have greater metastatic potential, as shown by recent studies revealing immunohistochemical and gene array changes [17,18]. Second, these studies provide indirect evidence that the Gleason grading system is reproducible across different institutions, as the correlations between GS and outcome variables are very similar.…”

Section: Discussionmentioning

confidence: 99%

Predictive value of primary Gleason pattern 4 in patients with Gleason score 7 tumours treated with radical prostatectomy

Khoddami¹,

Shariat²,

Lotan³

et al. 2004

BJU International

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RESULTSIn all, 215 patients (70%) had a final GS of 3 + 4 and 94 (30%) of 4 + 3. A final GS of 4 + 3 was associated with clinical stage T2 disease ( P = 0.024), a higher biopsy GS ( P < 0.001), seminal vesicle involvement ( P < 0.001), positive surgical margins ( P = 0.036), lymphovascular invasion ( P = 0.018), metastases to regional lymph nodes ( P = 0.008), higher preoperative serum prostate-specific antigen (PSA) ( P = 0.042), and percentage positive biopsy cores ( P = 0.006). In univariate analysis, patients with GS 4 + 3 had a significantly higher risk of biochemical progression than those with GS 3 + 4 ( P = 0.002). The 5-year actuarial risk of biochemical progression was 17% and 35% for GS 3 + 4 and 4 + 3, respectively ( P = 0.0016). In a standard postoperative multivariate analysis, only preoperative PSA and metastases to regional lymph nodes were associated with PSA progression ( P < 0.001 and 0.002, respectively). However, patients with final GS 4 + 3 had a shorter PSA doubling time after progression than those with GS 3 + 4 ( P = 0.009). CONCLUSIONSTumours with a final GS of 4 + 3 are more aggressive than GS 3 + 4 tumours. Recognising the distinction in GS 7 between predominant 4 vs 3 scores after radical prostatectomy should improve the ability of clinicians to counsel patients. The GS 4 pattern deserves further molecular study.

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“…Most of them suggest that immunohistochemical p53 positivity increases with high grade, advanced stage and peripheral zone origin. [3][4][5][6][7] Some studies have suggested that nuclear p53 accumulation may correlate with poor prognosis after radical prostatectomy, 8,9 external beam radiation, 10 and watchful waiting 11 but these data were not confirmed in other studies. [12][13][14] Perhaps some of these discordances were caused by the relatively small number of patients included in these studies ranging from 24-392 patients.…”

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confidence: 95%

Clinical significance of p53 alterations in surgically treated prostate cancers

et al. 2008

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Despite the high number of previous studies, the role of p53 alterations in prostate cancer is not clearly defined. To address the role of p53 alterations in prostate cancer biology, a total of 2514 cancers treated by radical prostatectomy were successfully analyzed by immunohistochemistry in a tissue microarray format. Overall a low rate of p53-positive tumors was found (2.5%). A significant underestimation of p53-positive cases was excluded by subsequent large section analyses and direct sequencing of the p53 gene in subsets of our patients. Large section analysis of 23 cases considered negative on the tissue microarray yielded only one weakly p53-positive tumor. Only 4 out of 64 (6.4%) high-grade tumors, that were considered negative for p53 by immunohistochemistry, presented exon 5-8 mutations. These data suggest a high sensitivity of our immunohistochemistry approach and confirm the overall low frequency of p53 alterations in clinically localized prostate cancer. A positive p53 immunostaining was strongly associated with presence of exon 5-8 mutations (Po0.0001), advanced pT-stage (Po0.0001), high Gleason grade (Po0.0001), positive surgical margins (P ¼ 0.03) and early biochemical tumor recurrence (Po0.0001). A higher rate of positive p53 immunostaining was detected in late-stage diseases including metastatic prostate cancer (P ¼ 0.0152) and hormone-refractory tumors (P ¼ 0.0003). Moreover, p53 expression was identified as an independent predictor of biochemical tumor recurrence in the subgroup of low-and intermediate-grade cancers. In summary, the results of this study show that p53 mutations characterize a small biologically aggressive subgroup of prostate cancers with a high risk of progression after prostatectomy. The rate of p53 alterations increases with prostate cancer progression.

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Characterisation of biomolecular profiles in primary high-grade prostate cancer treated by radical prostatectomy

Cited by 23 publications

References 35 publications

Prognostic relevance of Bcl‐2 overexpression in surgically treated prostate cancer is not caused by increased copy number or translocation of the gene

Prognostic relevance of Bcl‐2 overexpression in surgically treated prostate cancer is not caused by increased copy number or translocation of the gene

Predictive value of primary Gleason pattern 4 in patients with Gleason score 7 tumours treated with radical prostatectomy

Clinical significance of p53 alterations in surgically treated prostate cancers

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