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01.12.2018 | Research article | Ausgabe 1/2018 Open Access

BMC Cancer 1/2018

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

Zeitschrift:
BMC Cancer > Ausgabe 1/2018
Autoren:
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
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi: https://​doi.​org/​10.​1186/​s12885-017-3956-3) contains supplementary material, which is available to authorized users.

Abstract

Background

Breast cancer anti-estrogen resistance 1 (BCAR1/p130cas) is a hub for diverse oncogenic signaling cascades and promotes tumor development and progression.

Methods

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.

Results

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.

Conclusion

The results of our study identify BCAR1 as a prognostic biomarker with potential clinical value for risk stratification of ERG-negative prostate cancer.
Zusatzmaterial
Additional file 1: Figure S1. Kaplan-Meier plots of prostate specific antigen (PSA) recurrence after radical prostatectomy and negative or strong BCAR1 staining in subsets of all cancers defined by (a) classical Gleason score, (b-h) quantitative Gleason score defined by the percentage of Gleason 4 grade and (i-j) by the tertiary Gleason 5 grade. Figure S2. Kaplan-Meier plots of prostate specific antigen (PSA) recurrence after radical prostatectomy and BCAR1 staining in subsets of ERG negative cancers defined by (a) classical and (b-h) quantitative Gleason score, defined by the percentage of Gleason 4 grade and (i-j) by the tertiary Gleason 5 grade. Figure S3. Correlation of BCAR1 staining and androgen receptor (AR) staining in all cancers, Figure S4. Kaplan-Meier plot of prostate specific antigen (PSA) recurrence after radical prostatectomy and clinical stage in all cancers, Figure S5. Kaplan-Meier plot of prostate specific antigen (PSA) recurrence after radical prostatectomy and Gleason score at biopsy in all cancers, Table S1. Pathological and clinical data of the arrayed prostate cancer, Table S2. Association between BCAR1 staining and prostate cancer clinical characteristics in ERG–fusion negative and positive subsets, Table S3. Association between BCRA1 expression and Ki67-labeling index depending on ERG-fusion status in different Gleason scores. (DOC 5580 kb)
12885_2017_3956_MOESM1_ESM.doc
Literatur
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