Inactivation of myopodin expression associated with prostate cancer relapse

Abstract

Objectives Myopodin has recently been characterized as a tumor suppressor gene whose encoded product inhibits prostate cancer growth and metastasis both in vitro and in animal models. However, the clinical evidence of tumor suppression in humans is still lacking. In this study, we conducted a large-scale analysis of myopodin expression in prostate cancer samples to examine the relationship between myopodin expression and prostate cancer grade and stage and the probability of clinical relapse. Methods Immunostaining using anti-myopodin antibodies was performed on 746 formalin-fixed paraffin-embedded tissue samples to evaluate the level of myopodin expression in normal and malignant prostatic tissue. Results The expression of myopodin was semiquantitatively determined by immunostaining. The myopodin expression levels were examined in relation to prostate cancer grade and stage, preoperative prostate-specific antigen level, surgical margin involvement, tumor volume, and clinical relapse. The mean myopodin expression score (range 0 to 3) was 2.1 and 0.88 for benign prostatic tissue and prostate cancer, respectively. Minimal variation in myopodin expression was observed among the various grades, stages, tumor volumes, and preoperative prostate-specific antigen levels of prostate cancer. However, samples with positive surgical margins were associated with lower myopodin expression. Complete inactivation of myopodin expression correlated with a greater than 86% rate of clinical relapse. Conclusions Our results suggest that myopodin is an important predictor of prostate cancer metastasis, independent of Gleason score, preoperative prostate-specific antigen level, and tumor stage.