Machtens S, Serth J, Bokemeyer C, Bathke W, Minssen A, Kollmannsberger C, Hartmann J, Knüchel R, Kondo M, Jonas U, Kuczyk M
Department of Urology, Hannover University Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
Int J Cancer. 2001 Sep 20;95(5):337-42. doi: 10.1002/1097-0215(20010920)95:5<337::aid-ijc1059>3.0.co;2-1.
The serine protease inhibitor Maspin has been reported to inhibit the invasiveness and motility of prostate cancer tumor cells. Additionally, a p53-dependent regulatory pathway of Maspin in prostate cancer cell lines has been indicated. The first aim of our study was to determine the prognostic value of Maspin protein expression for the recurrence-free survival of patients undergoing radical prostatectomy for the treatment of clinically localized prostate cancer. Secondly, Maspin expression was correlated to p53 protein expression in order to gain additional information on a possible and previously suggested regulatory influence of the wild-type p53 protein on the Maspin protein expression. Tumor specimens obtained from 84 patients undergoing radical prostatectomy for localized prostate cancer were investigated for the expression of the Maspin and p53 protein by an immunohistochemic approach. Maspin protein expression was correlated with further patients' and tumor characteristics such as tumor stage, histologic grading, regional lymph node status, p53 protein expression and recurrence-free survival of the patients following radical prostatectomy. After a median follow-up of 64 months (24-197 months), 23 of 40 patients (58%) with a negative or decreased Maspin expression (group 1) developed local recurrence or systemic tumor progression in contrast to 8 of 44 patients (18%) with a retained expression of the Maspin protein (group 2) (p = 0.02; log-rank test). The median recurrence-free survival following radical prostatectomy was 26 months (12-37 months) for group 1 patients and 41 months (5-134 months) for patients from group 2 (p = 0.04). A positive immunohistochemic staining reaction for the p53 protein was significantly correlated with a decreased expression of the Maspin protein (p = 0.015; Spearman correlation coefficient). Additionally, loss of Maspin protein expression was correlated to higher tumor stages (p = 0.002) and an increasing histologic dedifferentiation (p = 0.03). This is the first study to indicate that Maspin protein possibly functions as a clinically relevant inhibitor of tumor progression, preventing the local invasiveness and further systemic progression of prostate cancer. Our investigation delivers first hints for a p53-dependent regulatory pathway of the Maspin protein in human prostate cancer.
丝氨酸蛋白酶抑制剂Maspin已被报道可抑制前列腺癌肿瘤细胞的侵袭性和运动性。此外，已表明在前列腺癌细胞系中存在一条Maspin的p53依赖性调节途径。我们研究的首要目的是确定Maspin蛋白表达对接受根治性前列腺切除术治疗临床局限性前列腺癌患者无复发生存的预后价值。其次，将Maspin表达与p53蛋白表达相关联，以便获取关于野生型p53蛋白对Maspin蛋白表达可能存在的、先前提出的调节影响的更多信息。通过免疫组织化学方法，对84例接受根治性前列腺切除术治疗局限性前列腺癌患者的肿瘤标本进行了Maspin和p53蛋白表达的研究。Maspin蛋白表达与患者的其他特征以及肿瘤特征相关，如肿瘤分期、组织学分级、区域淋巴结状态、p53蛋白表达以及根治性前列腺切除术后患者的无复发生存情况。在中位随访64个月（24 - 197个月）后，40例Maspin表达阴性或降低的患者中有23例（58%）（第1组）出现局部复发或全身肿瘤进展，相比之下，44例Maspin蛋白表达保留的患者中有8例（18%）（第2组）出现上述情况（p = 0.02；对数秩检验）。第1组患者根治性前列腺切除术后的中位无复发生存期为26个月（12 - 37个月），第2组患者为41个月（5 - 134个月）（p = 0.04）。p53蛋白的免疫组织化学染色阳性反应与Maspin蛋白表达降低显著相关（p = 0.015；Spearman相关系数）。此外，Maspin蛋白表达缺失与更高的肿瘤分期（p = 0.002）和组织学去分化增加（p = 0.03）相关。这是第一项表明Maspin蛋白可能作为肿瘤进展的临床相关抑制剂发挥作用，预防前列腺癌局部侵袭和进一步全身进展的研究。我们的研究为人类前列腺癌中Maspin蛋白的p53依赖性调节途径提供了初步线索。
