Validierung von Biomarkern für die Prognose des Prostatakarzinoms unter spezieller Berücksichtigung der intratumoralen Heterogenität und genomischen Instabilität

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Background: Prostate cancer risk classification systems in current use still rely only on clinicopathological parameters resulting in uncertainties in disease prognostication. To improve individual risk stratification, the predictive value of selected proteins involved in prostate cancer progression with respect to tumor heterogeneity and genomic instability was examined. Methods: The degree of genomic instability in 50 radical prostatectomy specimens by DNA-Image-Cytometry and evaluated protein expression was assessed immunohistochemically in related 199 tissue-microarray (TMA) cores for Special-AT-rich-binding-Protein-1 (SATB1), Spindlin-1 (SPIN1), Tropomyosin-4 (TPM4), Vimentin (VIME), and β-Tubulin (TBB5). Immunohistochemical data were correlated with the degree of genomic instability and established clinical risk factors e.g., postoperative Gleason Score (GS), preoperative PSA serum level, pathological tumor stage, and overall survival. Results: Genomic instability was associated with a GS≥7 (p=0.001) and worse overall survival (p=0.006). In contrast, a GS≤6 (p=0.040) and genomic stability (p=0.027) were associated with positive SATB1 expression, which was identified as predictor for increased overall survival (p=0.023, age-adjusted HR 0.413, 0.192 – 0.886). A high expression of SPIN1 was also associated with longer overall survival (p=0.048) and a lower preoperative PSA-value (p=0.047). The combination of SATB1 expression, degree of genomic instability, and GS assessment lead to a novel Prostate Cancer Prediction Score (PCP-Score) which outperforms the current D’Amico et al. stratification for predicting overall survival (p=0.001, age-adjusted HR 4, CI 1.701 – 9.407). Conclusion: Low SATB1 expression, genomic instability and GS≥7 were identified as markers for poor prognosis in prostate cancer patients. Their combination overcomes current clinical risk stratification regimes and could thus support individualized treatment decisions.

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Christoph Dumke

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Biomarker Cancerogen Karzinom Krebs Prostata Vorsteherdrüse

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