Identification of Combinatorial Genomic Abnormalities Associated with Prostate Cancer Early Recurrence

Multiple biomarkers are needed to distinguish aggressive from indolent prostate cancer. We tested the prognostic utility of a three-marker fluorescent in situ hybridization panel (TMPRSS2/ERG rearrangements, AR gain, and PTEN deletion) in a retrospective cohort (n = 210; median follow-up, 5.

7 years). PTEN deletion was associated with an increased risk of biochemical recurrence (BcR; hazard ratio, 3. 58; 95% CI, 1. 39-9. 22; P < 0. 01) by multivariable Cox regression analyses and earlier BcR (P < 0. 02) by Kaplan-Meier analysis. AR gain coexisted with X-chromosome gain and was associated with advanced tumor stage. When this panel was applied, two categories of combinatorial abnormalities proved clinically important. First, PTEN deletion without TMPRSS2/ERG rearrangement was enriched in pT3/4 tumors (70% versus 48%) with Gleason grades of 8 to 9 (60% versus 17%) compared with the entire cohort. These patients had earlier BcR than patients with normal fluorescent in situ hybridization panel results (P < 0. 01). In contrast, patients with PTEN deletion and ERG rearrangement had a BcR rate similar to patients who tested normal for all three markers (P > 0. 1). Second, AR gain and concurrent trisomy 10 without TMPRSS2/ERG rearrangement were enriched in pT3/4 tumors with Gleason grades of 8 to 9. The three-marker fluorescent in situ hybridization panel identified genomic aberrations associated with advanced disease state and early BcR in prostate cancer.

The Journal of molecular diagnostics : JMD. 2016 Jan 02 [Epub ahead of print]

Xiaoyu Qu, Claudio Jeldres, Lena Glaskova, Cynthia Friedman, Sarah Schroeder, Peter S Nelson, Christopher Porter, Min Fang

Fred Hutchinson Cancer Research Center, Seattle, Washington; Seattle Cancer Care Alliance, Seattle, Washington. , Department of Urology, University of Sherbrooke, Sherbrooke, Quebec, Canada. , Seattle Cancer Care Alliance, Seattle, Washington. , Seattle Cancer Care Alliance, Seattle, Washington. , Seattle Cancer Care Alliance, Seattle, Washington. , Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Washington, Seattle, Washington. , Virginia Mason Medical Center, Seattle, Washington. Fred Hutchinson Cancer Research Center, Seattle, Washington; Seattle Cancer Care Alliance, Seattle, Washington; University of Washington, Seattle, Washington. 

PubMed

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