High RNA-binding motif protein 3 expression is an independent prognostic marker in operated prostate cancer and tightly linked to ERG activation and PTEN deletions

Abstract

Background: The RNA-binding motif protein 3 (RBM3) has recently been suspected as a prognostic biomarker in several cancers.

Methods: RBM3 expression was analysed by immunohistochemistry on a tissue microarray containing 11,152 prostate cancers.

Results: RBM3 expression was more often detectable in malignant compared to benign prostate. RBM3 immunostaining was found in 64% of the interpretable prostate cancers and was considered strong in 25.6%. High RBM3 expression was linked to advanced tumour stage, high Gleason score, positive nodal involvement and positive surgical margin status (p<0.0001 each). There was a remarkable accumulation of strong RBM3 expression in v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) positive prostate cancers and tumours harbouring PTEN deletions (p<0.0001 each). Moreover, RBM3 staining was tightly related to early biochemical recurrence if all tumours or subgroups of ERG negative and ERG positive cancers were analysed (p<0.0001 each). In multivariate analysis, including RBM3 staining, Gleason grade, pT stage, prostate-specific antigen (PSA), surgical margin status, and nodal status, the prognostic impact of RBM3 staining retained statistically significance (p=0.0084).

Conclusion: Our observations indicate that high RBM3 expression is an independent prognostic marker in prostate cancer. The tight link to ERG activation and PTEN deletions suggest interaction with key molecular pathways in prostate cancer.

Keywords: ERG; PTEN; Prostate cancer; RBM3; TMA.