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- Title
High BCAR1 expression is linked to adverse tumour features and early PSA recurrence in ERG negative prostate cancers.
- Authors
Krech, Till; Heinemann, Nina; Hube-Magg, Claudia; Kluth, Martina; Minner, Sarah; Koop, Christina; Graefen, Markus; Heinzer, Hans; Tsourlakis, Maria Christina; Wittmer, Corinna; Huland, Hartwig; Simon, Ronald; Schlomm, Thorsten; Sauter, Guido; Steurer, Stefan; Grupp, Katharina
- Abstract
Objective: Breast cancer anti-estrogen resistance 1 (BCAR1/p130cas) is a hub for diverse oncogenic signaling cascades and promotes tumour development and progression. The current study aims to analyze the prevalence and prognostic impact of BCAR1 in prostate cancer. Methods: BCAR1 expression was analyzed by immunohistochemistry on a tissue microarray containing more than 11,000 prostate cancer specimens. Results were compared to tumour phenotype, biochemical recurrence, and molecular subtypes defined by ERG status as well as genomic deletions of 3p, 5q, 6q and PTEN. Date and results: BCAR1 immunostaining was detectable in 77.6% of 9,473 interpretable cancers and considered strong in 38.5%, moderate in 23.2% and weak in 15.8% of cases. High level BCAR1 expression were associated with high Gleason grade (p<0.0001), advanced pathological tumour stage (p=0.0013), lower preoperative PSA level (p<0.0001), increased cell proliferation (p<0.0001) and early PSA recurrence (p=0.0016). In subgroup analyses, these associations were largely driven by ERG-negative cancers. High level BCAR1 expression was also associated with TMPRSS2:ERG rearrangement and ERG expression (p<0.0001) and was linked to deletions of PTEN (p<0.0001), 6q (p=0.001) and 5q (p<0.0001) particularly in ERG negative cancers. The independent prognostic impact of BCAR1 was largely limited to ERG-negative cancers as revealed by multivariate analyses. Conclusions: BCAR1 is an independent prognosticator in ERG-negative prostate cancers and is associated with an adverse tumour phenotype in this subgroup. BCAR1 analysis might therefore be of clinical value for risk stratification of ERG-negative prostate cancer.
- Publication
Canadian Journal of Pathology, 2016, Vol 8, p14
- ISSN
1918-915X
- Publication type
Article