Department of Pathology, Istanbul University Cerrahpasa Medical School, 34098 Kocamustafapasa/Istanbul, Turkey.
J Cancer Res Clin Oncol. 2013 Aug;139(8):1373-82. doi: 10.1007/s00432-013-1453-x. Epub 2013 May 25.
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) participate in tumorigenesis, and their association with disease outcome is highly controversial. The present study investigates the influence of MMP-1, MMP-9 and TIMP-2 on different clinicopathologic variables and disease-free survival (DFS) of patients with prostate carcinoma.
Hundred and forty-five cases are included in the study, and levels of MMP/TIMP expressions are assessed in three tissue compartments (i.e., tumor, stroma and normal glands) with immunohistochemistry.
Matrix metalloproteinase-1 expression in tumor cells was associated with lower Gleason scores, pretreatment prostate-specific antigen levels and lower incidence of vascular, perineural and extracapsular invasions. Moreover, MMP-9 positivity and TIMP-2 expression in normal glands were correlated with lower Gleason patterns and early stage at presentation. Expression of MMP in tumor cells and the presence of TIMP-2 in normal glands were associated with better DFS.
Variability of MMP/TIMP expressions from case to case makes it difficult to evaluate their impact on clinical outcome. However, these proteins might be new and promising targets for prostate cancer therapy in the future.
基质金属蛋白酶(MMPs)和金属蛋白酶组织抑制剂(TIMPs)参与肿瘤的发生,其与疾病结局的关系存在很大争议。本研究探讨了 MMP-1、MMP-9 和 TIMP-2 对前列腺癌患者不同临床病理变量和无病生存(DFS)的影响。
本研究纳入 145 例病例,采用免疫组织化学方法评估 MMP/TIMP 表达在肿瘤、基质和正常腺体三个组织区室中的水平。
肿瘤细胞中 MMP-1 的表达与较低的 Gleason 评分、治疗前前列腺特异性抗原水平以及血管、神经周围和包膜外侵犯的发生率较低相关。此外,正常腺体中 MMP-9 的阳性和 TIMP-2 的表达与较低的 Gleason 模式和早期发病相关。肿瘤细胞中 MMP 的表达和正常腺体中 TIMP-2 的存在与更好的 DFS 相关。
MMP/TIMP 表达的个体差异使得评估它们对临床结局的影响变得困难。然而,这些蛋白可能是未来前列腺癌治疗的新的有前途的靶点。