Chromatin changes predict recurrence after radical prostatectomy.

BACKGROUND - Pathological evaluations give the best prognostic markers for prostate cancer patients after radical prostatectomy, but the observer variance is substantial. These risk assessments should be supported and supplemented by objective methods for identifying patients at increased risk of recurrence.

Markers of epigenetic aberrations have shown promising results in several cancer types and can be assessed by automatic analysis of chromatin organisation in tumour cell nuclei.

METHODS - A consecutive series of 317 prostate cancer patients treated with radical prostatectomy at a national hospital between 1987 and 2005 were followed for a median of 10 years (interquartile range, 7-14). On average three tumour block samples from each patient were included to account for tumour heterogeneity. We developed a novel marker, termed Nucleotyping, based on automatic assessment of disordered chromatin organisation, and validated its ability to predict recurrence after radical prostatectomy.

RESULTS - Nucleotyping predicted recurrence with a hazard ratio (HR) of 3.3 (95% confidence interval (CI), 2.1-5.1). With adjustment for clinical and pathological characteristics, the HR was 2.5 (95% CI, 1.5-4.1). An updated stratification into three risk groups significantly improved the concordance with patient outcome compared with a state-of-the-art risk-stratification tool (P<0.001). The prognostic impact was most evident for the patients who were high-risk by clinical and pathological characteristics and for patients with Gleason score 7.

CONCLUSIONS - A novel assessment of epigenetic aberrations was capable of improving risk stratification after radical prostatectomy.British Journal of Cancer advance online publication 28 April 2016; doi:10.1038/bjc.2016.96 www.bjcancer.com.

British journal of cancer. 2016 Apr 28 [Epub ahead of print]

Tarjei S Hveem, Andreas Kleppe, Ljiljana Vlatkovic, Elin Ersvær, Håkon Wæhre, Birgitte Nielsen, Marte Avranden Kjær, Manohar Pradhan, Rolf Anders Syvertsen, John Arne Nesheim, Knut Liestøl, Fritz Albregtsen, Håvard E Danielsen

Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo NO-0424, Norway., Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo NO-0424, Norway., Department of Pathology, Oslo University Hospital, Oslo NO-0424, Norway., Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo NO-0424, Norway., Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo NO-0424, Norway., Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo NO-0424, Norway., Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo NO-0424, Norway., Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo NO-0424, Norway., Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo NO-0424, Norway., Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo NO-0424, Norway., Department of Informatics, University of Oslo, Oslo NO-0316, Norway., Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo NO-0424, Norway., Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo NO-0424, Norway.

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