Prognostic significance of Runx2, Msx2 and osteocalcin expressions in prostate cancer

Abstract

Bone metastasis is a predominant event in advanced prostate cancer patients. Identification of primary cancers with metastatic potential is essential for prognosis and management of this disease. Recently, several bone formation-related markers have been suggested to facilitate cancer cell growth in the bone in several types of tumours. The aim of this study was to investigate the prognostic significance of three bone formation-related proteins, Runx2, Msx2 and osteocalcin, in prostate cancer. Using 128 prostate cancer specimens as well as 8 cases of high-grade prostatic intraepithelial neoplasia (PIN) and 39 benign prostatic hyperplasia (BPH) samples, we first compared the expression patterns of these three proteins between non-malignant and cancer tissues by immunohistochemistry. Then, we compared the Runx2, Msx2 and osteocalcin expression levels between the cancer specimens with or without metastatic potential to study if they could be used as prognostic markers for prostate cancer metastasis. Furthermore, we also studied the association between Runx2, Msx2 and osteocalcin expressions, and Gleason score of the prostate cancer specimens as well as preoperative serum PSA (prostatic specific antigen) levels to investigate their correlation with tumour progression. Our results showed that the nuclear expression of Runx2 was significantly higher in the prostate cancer specimens than the non-malignant tissues (p <0.001) and its expression levels were positively associated with both Gleason grading (p=0.008) and metastatic potential of prostate cancer (p <0.001). In contrast, the nuclear staining of Msx2 was much lower in the prostate cancer specimens compared to the non-malignant tissues (p <0.001), while its expression levels were markedly associated with metastatic potential (p <0.01). In addition, we found that osteocalcin staining was mainly detected in the cytoplasm of the prostate epithelial cells, and significant difference of the staining intensity was observed between non-malignant and prostate cancer specimens (p <0.001). However, there was no significant difference in osteocalcin immunostainings between the cancer specimens with or without metastatic potential. We also found that the nuclear expression of Runx2 was correlated significantly with Msx2 nuclear expression (p=0.001) and osteocalcin cytoplasmic expression (p=0.043) in prostate cancer specimens. Lastly, only Runx2 nuclear staining showed positive correlation with preoperative serum PSA levels (p <0.01). Taken together, our results have demonstrated the prognostic value of Runx2, Msx2 and osteocalcin expressions in prostate cancer and suggested a group of novel markers for the prediction of metastatic progression in prostate cancer patients.