Institute of Pathology, Charité University Hospital, Berlin, Germany. d.wittschieber @ gmx.de
Pathobiology. 2011;78(3):123-31. doi: 10.1159/000323563. Epub 2011 May 26.
Urothelial bladder carcinomas show a divergent biological behavior, which significantly complicates risk stratification and clinical management. The MMP repressor RECK and the MMP activator EMMPRIN regulate the invasive potential by metalloproteinase-induced stromal degradation. Data on RECK in urothelial bladder cancer are lacking and information on EMMPRIN is sparse. This study aims to investigate the expression of RECK and EMMPRIN in urothelial carcinoma of the bladder and to correlate these findings with clinicopathological parameters.
Our study included 127 specimens of urothelial carcinomas derived from 103 patients who underwent either TUR-B or cystectomy. Immunohistochemical expression analysis was performed for RECK, EMMPRIN, MMP-2, MMP-9 and MMP-14. Expression levels were graded for staining intensity and correlated with pT stage and WHO tumor grade.
Invasive (≥pT1) as well as WHO high-grade urothelial carcinomas showed a statistically significant and stepwise downregulation of RECK (p < 0.001) and concomitant upregulation of EMMPRIN (p < 0.001) compared to non-invasive and WHO low-grade tumors. No correlation was observed for the MMPs investigated.
Decreased RECK and increased EMMPRIN expression are associated with increasing stage and grade. Both proteins may serve as molecular marker for the distinction between potentially invasive (≥pT1) and non-invasive tumors (≤pTa).
尿路上皮膀胱癌表现出不同的生物学行为，这极大地增加了风险分层和临床管理的复杂性。MMP 抑制剂 RECK 和 MMP 激活剂 EMMPRIN 通过金属蛋白酶诱导的基质降解来调节侵袭潜能。关于尿路上皮膀胱癌中 RECK 的数据缺乏，而关于 EMMPRIN 的信息也很有限。本研究旨在调查 RECK 和 EMMPRIN 在膀胱尿路上皮癌中的表达，并将这些发现与临床病理参数相关联。
我们的研究包括 103 例接受 TUR-B 或膀胱切除术的患者的 127 份尿路上皮癌标本。对 RECK、EMMPRIN、MMP-2、MMP-9 和 MMP-14 进行免疫组织化学表达分析。根据染色强度对表达水平进行分级，并与 pT 分期和 WHO 肿瘤分级相关联。
与非侵袭性和 WHO 低分级肿瘤相比，侵袭性（≥pT1）和 WHO 高级别尿路上皮癌中 RECK（p<0.001）和 EMMPRIN（p<0.001）的表达呈统计学显著和逐步下调。未观察到所研究的 MMP 之间存在相关性。
RECK 表达降低和 EMMPRIN 表达增加与分期和分级增加相关。这两种蛋白都可以作为潜在侵袭性（≥pT1）和非侵袭性肿瘤（≤pTa）之间的区分的分子标志物。
