Abstract 3180: Deletions of 18q characterizes a subset of aggressive prostate cancers with metastatic potential

Abstract

Abstract Large chromosomal deletions and rearrangements of the TMPRSS:ERG locus are hallmarks of prostate cancer. Deletion of 18q is recurrently found in prostate cancer, but the prevalence and clinical significance of this alteration have not been studied in detail as to yet. We took advantage of our large prostate cancer prognosis tissue microarray (TMA) containing more than 12,000 prostate cancers with clinical follow-up data and performed fluorescence in situ hybridization (FISH) analysis using an 18q21 probe. A total of 6,881 prostate cancers were interpretable by FISH. Deletion of 18q was found in 7.5% of cancers, and was linked to advanced tumor stage (p<0.0001), high Gleason grade (p = 0.0013) and biochemical recurrence (BCR, p<0.0001). Comparison with data from TMPRSS:ERG fusion and ERG protein expression revealed that deletions of 18q were only marginally related to an ERG-fusion negative phenotype (p = 0.0063). Multivariate analysis showed that the prognostic value of 18q deletion was independent from the established prognostic factors in all cancers (p = 0.0004) as well as in the subsets of ERG-fusion negative (p = 0.0148) and ERG-fusion positive cancers (p = 0.0264). From the clinical data attached to our TMA, we defined additional clinical endpoints beyond BCR, which represent the four hallmarks (local, local invasive, occult systemic and metastatic) of tumor growth and dissemination in prostate cancer. Deletion of 18q was linked to unfavorable outcome also according to these alternative clinical endpoints. For example, the fraction of cancers with occult systemic or metastatic dissemination increased from 33.6% in patients whose tumors lacked 18q deletion to 41.8% in patients with tumors harboring 18q deletion (p = 0.0458). In summary, the results of our study demonstrate a pivotal role of 18q deletions for prognosis in prostate cancer independent of the established prognosticators. Citation Format: Claudia Hube-Magg, Martina Kluth, Maximilian Graunke, Christina Koop, Steuber Thomas, Markus Graefen, Stefan Steurer, Thorsten Schlomm, Guido Sauter, Ronald Simon. Deletions of 18q characterizes a subset of aggressive prostate cancers with metastatic potential. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3180.