Hofer Matthias D, Kuefer Rainer, Varambally Sooryanarayana, Li Haojie, Ma Jing, Shapiro Geoffrey I, Gschwend Juergen E, Hautmann Richard E, Sanda Martin G, Giehl Klaudia, Menke Andre, Chinnaiyan Arul M, Rubin Mark A
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Cancer Res. 2004 Feb 1;64(3):825-9. doi: 10.1158/0008-5472.can-03-2755.
Distinguishing aggressive prostate cancer from indolent disease represents an important clinical challenge, as current therapy requires over treating men with prostate cancer to prevent the progression of a few cases. Expression of the metastasis-associated protein 1 (MTA1) has previously been found to be associated with progression to the metastatic state in various cancers. Analyzing DNA microarray data, we found MTA1 to be selectively overexpressed in metastatic prostate cancer compared with clinically localized prostate cancer and benign prostate tissue. These results were validated by demonstrating overexpression of MTA1 in metastatic prostate cancer by immunoblot analysis. MTA1 protein expression was evaluated by immunohistochemistry in a broad spectrum of prostate tumors with tissue microarrays containing 1940 tissue cores from 300 cases. Metastatic prostate cancer demonstrated significantly higher mean MTA1 protein expression intensity (score = 3.4/4) and percentage of tissue cores staining positive for MTA1 (83%) compared with clinically localized prostate cancer (score = 2.8/4, 63% positive cores) or benign prostate tissue (score = 1.5/4, 25% positive cores) with a mean difference of 0.54 and 1.84, respectively (P < 0.00001 for both). Paradoxically, for localized disease, higher MTA1 protein expression was associated with lower rates of prostate specific antigen recurrence after radical prostatectomy for localized disease. In summary, this study identified an association of MTA1 expression and prostate cancer progression.
区分侵袭性前列腺癌和惰性疾病是一项重要的临床挑战，因为目前的治疗需要对前列腺癌患者进行过度治疗，以防止少数病例的进展。先前已发现转移相关蛋白1（MTA1）的表达与多种癌症向转移状态的进展有关。通过分析DNA微阵列数据，我们发现与临床局限性前列腺癌和良性前列腺组织相比，MTA1在转移性前列腺癌中选择性过表达。通过免疫印迹分析证实转移性前列腺癌中MTA1的过表达，从而验证了这些结果。使用包含来自300例病例的1940个组织芯的组织微阵列，通过免疫组织化学评估了广泛的前列腺肿瘤中的MTA1蛋白表达。与临床局限性前列腺癌（评分=2.8/4，63%阳性芯）或良性前列腺组织（评分=1.5/4，25%阳性芯）相比，转移性前列腺癌显示出显著更高的平均MTA1蛋白表达强度（评分=3.4/4）和MTA1染色阳性的组织芯百分比（83%），平均差异分别为0.54和1.84（两者P<0.00001）。矛盾的是，对于局限性疾病，较高的MTA1蛋白表达与局限性疾病根治性前列腺切除术后前列腺特异性抗原复发率较低相关。总之，本研究确定了MTA1表达与前列腺癌进展之间的关联。
