High BCAR1 expression is associated with early PSA recurrence in ERG negative prostate cancer

Asmus Heumann, Nina Heinemann, Claudia Hube-Magg, Dagmar S. Lang, Katharina Grupp, Martina Kluth, Sarah Minner, Christina Möller-Koop, Markus Graefen, Hans Heinzer, Maria Christina Tsourlakis, Waldemar Wilczak, Corinna Wittmer, Frank Jacobsen, Hartwig Huland, Ronald Simon, Thorsten Schlomm, Guido Sauter, Stefan Steurer, Patrick Lebok, Andrea Hinsch

Breast cancer anti-estrogen resistance 1 (BCAR1/p130cas) is a hub for diverse oncogenic signaling cascades and promotes tumor development and progression. To understand the effect of BCAR1 in prostate cancer, we analyzed its expression on more than 11,000 prostate cancer samples. BCAR1 expression levels were compared with clinical characteristics, PSA recurrence, molecular subtype defined by ERG status and 3p, 5q, 6q and PTEN deletion. BCAR1 staining was barely detectable in normal prostate glands but seen in 77.6% of 9472 interpretable cancers, including strong expression in 38.5%, moderate in 23.2% and weak in 15.9% of cases. BCAR1 up regulation was associated with positive ERG status (p < 0.0001), high Gleason score (p < 0.0001), advanced pathological tumor stage (p = 0.0082), lower preoperative PSA level (p < 0.0001), increased cell proliferation (p < 0.0001), early PSA recurrence (p = 0.0008), and predicted prognosis independently from clinico-pathological parameters available at the time of the initial biopsy. However, subset analyses revealed that the prognostic impact of BCAR1 expression was limited to ERG-negative cancer. That BCAR1 up regulation was linked to almost all analyzed deletions (p < 0.0001 each for PTEN, 5q, 6q deletion) may suggest a functional link to genomic instability. The results of our study identify BCAR1 as a prognostic biomarker with potential clinical value for risk stratification of ERG-negative prostate cancer.