RECK表达降低表明前列腺癌中蛋白水解失衡,这与更高的肿瘤侵袭性以及根治性前列腺切除术后前列腺特异性抗原复发风险相关。
Decreased RECK expression indicating proteolytic imbalance in prostate cancer is associated with higher tumor aggressiveness and risk of prostate-specific antigen relapse after radical prostatectomy.
作者信息
Rabien Anja, Burkhardt Mick, Jung Monika, Fritzsche Florian, Ringsdorf Martin, Schicktanz Hanka, Loening Stefan A, Kristiansen Glen, Jung Klaus
机构信息
Department of Urology, Charité University Medicine, Humboldt University, Schumannstrasse 20/21, D-10098 Berlin, Germany.
出版信息
Eur Urol. 2007 May;51(5):1259-66. doi: 10.1016/j.eururo.2006.05.050. Epub 2006 Jun 14.
OBJECTIVES
Decreased expression of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) was recently shown in several cancer types. To evaluate its potential role for prostate carcinoma, we investigated RECK expression in prostate cancer (pCA) samples.
METHODS
RECK messenger RNA levels in 15 microdissected normal/tumor matches were determined by quantitative reverse transcriptase-polymerase chain reaction. Protein expression of RECK was evaluated by immunohistochemical staining in tissue samples of adenomectomies (n=24) and pCA samples after radical prostatectomy (n=247). RECK expression was related to preoperative prostate-specific antigen (PSA), tumor stage and grade, surgical margin status, and PSA relapse-free time after radical prostatectomy.
RESULTS
Consistent with lower RECK messenger RNA by 24%, RECK protein expression was decreased in pCA, compared with adjacent normal tissue and prostatic intraepithelial neoplasia. RECK expression in samples of benign prostatic hyperplasia from adenomectomy specimens was higher than in normal adjacent tissue of prostate carcinomas. Decreased RECK expression was associated with higher Gleason score (> or =7) and higher tumor stage. Multivariate analysis using the Cox proportional hazards model revealed that negative RECK expression was an independent prognostic factor for an increased risk of PSA relapse, especially in patients with higher tumor grades (Gleason score > or =7).
CONCLUSIONS
Decreased RECK expression correlating with the aggressiveness of pCA and the PSA relapse-free time could become an adjunct tissue biomarker to improve the follow-up and treatment decision for these pCA patients.
目的
近期研究表明,富含Kazal基序的逆转诱导性富含半胱氨酸蛋白(RECK)在多种癌症类型中表达降低。为评估其在前列腺癌中的潜在作用,我们对前列腺癌(pCA)样本中的RECK表达进行了研究。
方法
通过定量逆转录聚合酶链反应测定15对显微切割的正常/肿瘤配对样本中的RECK信使核糖核酸水平。通过免疫组织化学染色评估腺瘤切除术组织样本(n = 24)和根治性前列腺切除术后pCA样本(n = 247)中RECK的蛋白表达。RECK表达与术前前列腺特异性抗原(PSA)、肿瘤分期和分级、手术切缘状态以及根治性前列腺切除术后的PSA无复发生存时间相关。
结果
与RECK信使核糖核酸降低24%一致,与相邻正常组织和前列腺上皮内瘤变相比,pCA中RECK蛋白表达降低。腺瘤切除标本中良性前列腺增生样本的RECK表达高于前列腺癌相邻正常组织。RECK表达降低与更高的Gleason评分(≥7)和更高的肿瘤分期相关。使用Cox比例风险模型进行的多变量分析显示,RECK表达阴性是PSA复发风险增加的独立预后因素,尤其是在肿瘤分级较高(Gleason评分≥7)的患者中。
结论
RECK表达降低与pCA的侵袭性及PSA无复发生存时间相关,可能成为一种辅助组织生物标志物,以改善这些pCA患者的随访和治疗决策。