Yu Yan Ping, Tseng George C, Luo Jian-Hua
Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Urology. 2006 Sep;68(3):578-82. doi: 10.1016/j.urology.2006.03.027. Epub 2006 Sep 18.
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.
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.
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.
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.
肌动蛋白结合蛋白最近被鉴定为一种肿瘤抑制基因,其编码产物在体外和动物模型中均能抑制前列腺癌的生长和转移。然而,在人类中肿瘤抑制的临床证据仍然缺乏。在本研究中,我们对前列腺癌样本中的肌动蛋白结合蛋白表达进行了大规模分析,以研究肌动蛋白结合蛋白表达与前列腺癌分级、分期以及临床复发概率之间的关系。
使用抗肌动蛋白结合蛋白抗体对746份福尔马林固定石蜡包埋组织样本进行免疫染色,以评估正常和恶性前列腺组织中肌动蛋白结合蛋白的表达水平。
通过免疫染色对肌动蛋白结合蛋白的表达进行半定量测定。研究了肌动蛋白结合蛋白表达水平与前列腺癌分级、分期、术前前列腺特异性抗原水平、手术切缘受累情况、肿瘤体积和临床复发之间的关系。良性前列腺组织和前列腺癌的肌动蛋白结合蛋白平均表达评分(范围为0至3)分别为2.1和0.88。在前列腺癌的不同分级、分期、肿瘤体积和术前前列腺特异性抗原水平之间,肌动蛋白结合蛋白表达的变化极小。然而,手术切缘阳性的样本与较低的肌动蛋白结合蛋白表达相关。肌动蛋白结合蛋白表达完全失活与超过86%的临床复发率相关。
我们的结果表明,肌动蛋白结合蛋白是前列腺癌转移的重要预测指标,独立于 Gleason评分、术前前列腺特异性抗原水平和肿瘤分期。