Laboratory of Medical Investigation-LIM55, Urology Department, University of Sao Paulo Medical School, Sao Paulo, Brazil.
Int Braz J Urol. 2012 Mar-Apr;38(2):167-74. doi: 10.1590/s1677-55382012000200004.
Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their regulators. The purpose of this study was to investigate whether MMP-2 and its specifi c regulators, TIMP-2, MT1-MMP and IL-8, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis and clinical outcome of prostate cancer (PCa).
MMP-2, TIMP-2, MT1-MMP and IL-8 expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in freshly frozen malignant and benign tissue specimens collected from 79 patients with clinically localized PCa who underwent radical prostatectomies. The control group consisted of 11 patients with benign prostate hyperplasia (BPH). The expression profile of the MMP-2 and its regulators were compared using Gleason scores, pathological stage, pre-operative PSA levels and the fi nal outcome of the PCa.
The analysis of 79 specimens of PCa revealed that MMP-2, TIMP-2, MT1-MMP and IL-8 were underexpressed at 60.0%, 72.2%, 62.0% and 65.8%, respectively, in malignant prostatic tissue in relation to BPH samples. Considering the prognostic parameters, we demonstrated that high Gleason score tumors (≥ 7) overexpressed MMP-2 (p = 0.048) and TIMP-2 (p = 0.021), compared to low Gleason score tumors (< 7).
We have demonstrated that MMP-2 and its regulators are underexpressed in PCa. Alternatively, overexpression of MMP-2 and TIMP-2 was related to higher Gleason score tumors. We postulate that alterations in metalloproteinase expression may be important in the control of tissue homeostasis related to prostate carcinogenesis and tumor behavior.
细胞外基质的动态平衡是通过基质金属蛋白酶（MMPs）及其调控因子的表达来严格维持的。本研究旨在探讨 MMP-2 及其特异性调节因子 TIMP-2、MT1-MMP 和 IL-8 是否以可重复的特异性模式表达，以及这些谱是否与前列腺癌（PCa）的预后和临床结局相关。
通过定量实时聚合酶链反应（qRT-PCR）分析 79 例接受根治性前列腺切除术的临床局限性 PCa 患者新鲜冷冻的恶性和良性组织标本中 MMP-2、TIMP-2、MT1-MMP 和 IL-8 的表达水平。对照组由 11 例良性前列腺增生（BPH）患者组成。比较 MMP-2 及其调节因子的表达谱与 Gleason 评分、病理分期、术前 PSA 水平和 PCa 的最终结果。
对 79 例 PCa 标本的分析表明，与 BPH 样本相比，恶性前列腺组织中 MMP-2、TIMP-2、MT1-MMP 和 IL-8 的表达分别下调了 60.0%、72.2%、62.0%和 65.8%。考虑到预后参数，我们发现高 Gleason 评分（≥7）肿瘤（p=0.048）和 TIMP-2 过表达（p=0.021）比低 Gleason 评分（<7）肿瘤过表达。
我们已经证明 MMP-2 及其调节因子在 PCa 中表达下调。相反，MMP-2 和 TIMP-2 的过表达与较高的 Gleason 评分肿瘤有关。我们推测，金属蛋白酶表达的改变可能在控制与前列腺癌发生和肿瘤行为相关的组织动态平衡方面具有重要意义。
