Högner Anica, Krause Hans, Jandrig Burkhard, Kasim Mumtaz, Fuller Tom Florian, Schostak Martin, Erbersdobler Andreas, Patzak Andreas, Kilic Ergin
Charité-Universitätsmedizin Berlin, Institut für Vegetative Physiologie, Charitéplatz 1, Berlin, Germany.
Charité-Universitätsmedizin Berlin, Klinik für Urologie, Charitéplatz 1, Berlin, Germany.
Urol Oncol. 2018 Mar;36(3):94.e1-94.e14. doi: 10.1016/j.urolonc.2017.10.027. Epub 2017 Nov 21.
To identify the clinicopathological association of PBRM1 (Polybromo-1 gene) and VHL (von Hippel-Lindau gene) expression at mRNA and protein levels in clear cell renal cell carcinoma (ccRCC) and its role in tumor progression.
Immunohistochemical analysis, Western blotting and qPCR analysis of PBRM1 and VHL were performed on fresh-frozen ccRCC and adjacent normal tissue obtained from 70 patients who underwent radical nephrectomy. In addition, a tissue microarray (TMA) from specimens of 326 ccRCC patients was used to evaluate the effect of loss of PBRM1 and VHL immunohistological expression on clinicopathological features as well as patient survival.
In frozen tissue, PBRM1 and VHL mRNA were significantly down-regulated in most ccRCC tumors (77.6%/80.6%). Simultaneous weak PBRM1 and VHL protein expression was observed in 21.4% of frozen tumors. In the TMA samples, weak PBRM1 and VHL immunohistochemical staining was observed in 60.4% of the cases and was correlated (P<0.001). The association of PBRM1 and VHL immunohistochemical expression with clinicopathological parameters depicts a variable picture: predominantly weak PBRM1 and VHL expression were significantly associated with higher Fuhrman grade (P = 0.012 and 0.024, respectively) but only weak VHL expression was associated with a higher pT stage (P = 0.023). PBRM1 expression did not affect the overall survival, whereas weak VHL expression was associated with decreased patient overall survival (P = 0.013).
Our data suggest that reduced expression of PBRM1 and VHL is correlated with an increased tumor aggressiveness. Low VHL expression was identified as a risk factor for worse patient overall survival, independently from PBRM1 expression pattern.
确定在透明细胞肾细胞癌（ccRCC）中，PBRM1（多溴-1基因）和VHL（冯·希佩尔-林道基因）在mRNA和蛋白质水平的表达与临床病理特征的关联及其在肿瘤进展中的作用。
对70例行根治性肾切除术患者的新鲜冷冻ccRCC及癌旁正常组织进行PBRM1和VHL的免疫组织化学分析、蛋白质印迹法及定量聚合酶链反应（qPCR）分析。此外，使用326例ccRCC患者标本的组织芯片（TMA）评估PBRM1和VHL免疫组织化学表达缺失对临床病理特征及患者生存的影响。
在冷冻组织中，大多数ccRCC肿瘤（77.6%/80.6%）中PBRM1和VHL mRNA显著下调。21.4%的冷冻肿瘤中同时观察到PBRM1和VHL蛋白表达较弱。在TMA样本中，60.4%的病例观察到PBRM1和VHL免疫组织化学染色较弱，且二者相关（P<0.001）。PBRM1和VHL免疫组织化学表达与临床病理参数的关联呈现出不同情况：主要是PBRM1和VHL表达较弱分别与较高的富尔曼分级显著相关（分别为P = 0.012和0.024），但只有VHL表达较弱与较高的pT分期相关（P = 0.023）。PBRM1表达不影响总生存期，而VHL表达较弱与患者总生存期降低相关（P = 0.013）。
我们的数据表明，PBRM1和VHL表达降低与肿瘤侵袭性增加相关。低VHL表达被确定为患者总生存期较差的危险因素，独立于PBRM1表达模式。
