One of the common features in advanced
prostate cancer is bone
metastasis. In this study, we investigated the clinical relevance of a bone factor, MSX2, in predicting the metastatic ability of prostate
adenocarcinoma. Evaluation of MSX2 expression was performed using prostate cell lines as well as patient specimens. A sharp decrease in MSX2 was found in primary
prostate cancer cells, 22Rv1, when compared with the non-malignant counterparts, followed by a gradual increase in more aggressive
prostate cancer cell lines. Interestingly, the
MSX2 protein was upregulated and predominantly expressed in the nucleus in aggressive
prostate cancer cell line, C4-2b, compared with the less aggressive 22Rv1. Consistent with the in vitro results, MSX2 nuclear expression was significantly higher in nodular
hyperplasia when compared with high-grade
prostatic intraepithelial neoplasia (PIN), while MSX2 nuclear expression in prostate
adenocarcinoma was higher than that in high-grade PIN. Importantly, MSX2 expression was increased significantly in
tumors with
metastasis compared with those without
metastasis. Finally, MSX2 nuclear scores were significantly increased in patients with preoperative serum PSA >20 ng/mL. No correlation between MSX2 nuclear score and Gleason score was found. Taken together, MSX2 may serve as a potential
biomarker in predicting primary prostate
tumors with higher metastatic capability.