Our results demonstrate that RBM3, while rarely expressed in normal prostatic gland epithelium, is up-regulated in PIN and invasive prostate cancer, and that patients with tumours expressing high nuclear levels of RMB3 have a significantly prolonged time to biochemical recurrence and clinical progression, also after adjustment for conventional prognostic factors. These findings are in line with previous findings in breast cancer [
11], ovarian cancer [
15], malignant melanoma [
16] and colorectal cancer (Hjelm et al, Proteomics Clinical Applications, in press). Thus, there are increasing evidence for RBM3 being a biomarker of good prognosis in multiple cancer forms. The mechanisms behind these findings remain to be elucidated, an undertaking that might be somewhat challenging as current in vitro data point towards a proto-oncogenic role for RBM3 [
8,
9,
19] and, hence, do not readily seem to support the clinical situation. However, the common hypothesis that oncogene activation is associated with an aggressive tumour phenotype does not always hold true, as well exemplified by the association between microsatellite instability and good prognosis in colorectal cancer [
20]. It is evident that RBM3, while sparsely expressed in normal tissue, is up-regulated in most cancer forms and their pre-invasive stages
in vivo. In light of the recently proposed association between RBM3 and DNA integrity in ovarian cancer [
17], it could be speculated that RBM3 might play an important role in promoting early stages of tumourigenesis by interfering with the anti-cancer barrier provided by various DNA damage checkpoint mechanisms [
21‐
23]. On the other hand, once a tumour has been established, an attenuated capability of DNA-damage response caused by RBM3 over expression might hinder the pressure for selection of more malignant clones [
21,
22]. Further studies are warranted to explore these associations.
In this study, we used a well-validated monoclonal antibody for detection of RBM3 expression [
15,
16]. Immunohistochemistry has several advantages compared to other assays in that it can easily be incorporated into clinical protocols and allows for assessment of the subcellular localization of proteins, which might have important prognostic implications. Our results indicate that immunohistochemical assessment of RBM3 expression in formalin-fixed paraffin embedded tumour samples could be a useful tool for prognostication and treatment stratification of prostate cancer patients. Since this was a small study these findings should be further validated in larger studies, preferably tumours from prospective, clinical trials.