Prognostic significance of altered p120ctn expression in bladder cancer

IF 4.4 2区医学 Q1 UROLOGY & NEPHROLOGY BJU International Pub Date : 2007-10-08 DOI:10.1111/j.1464-410X.2007.07264.x

Brasil Silva Neto, Gjanje L. Smith, Jessica A. Mandeville, Alex J. Vanni, Chad Wotkowicz, Kimberly M. Rieger-Christ, Egbert Baumgart, Micah A. Jacobs, Michael S. Cohen, Ron Zeheb, Massimo Loda, John A. Libertino, Ian C. Summerhayes

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引用次数: 17

Abstract

OBJECTIVE

To identify the frequency of change in the expression and localization of p120^ctn in bladder tumours and its association with clinical outcomes, and to investigate the potential role of p120^ctn in the migratory and invasive behaviour of bladder carcinoma cells.

MATERIALS AND METHODS

In all, 425 superficial tumour specimens (Ta, Tis and T1) and 305 invasive (T2–T4) tumour specimens from 534 patients were assembled in 10 tissue microarrays. P120^ctn immunostaining was scored for intensity and cellular localization and correlated with clinical variables and survival analysis. Knockdown of p120^ctn was achieved using small-interference RNA (siRNA) followed by the assessment of migration and invasion behaviour in standard in vitro assays.

RESULTS

The expression levels of p120 catenin inversely correlated with pathological tumour stage (P < 0.001), histological grade (P < 0.001), presence of lymphovascular invasion (P = 0.02) but not lymph node (LN) involvement (P = 0.17). Non-membranous localization of p120^ctn correlated with stage (P < 0.001), grade (P < 0.001), lymphovascular invasion (P = 0.04) and LN-positive disease (P = 0.02). A low expression level of p120^ctn was linked to a poor outcome in cancer-specific survival analysis. Knockdown of p120^ctn using siRNA resulted in a significant reduction in the migration and invasive potential of bladder carcinoma cells.

CONCLUSIONS

Our findings suggest that p120^ctn acts as a prognostic factor in bladder tumours and has a primary role to play in the migratory and invasive behaviour of bladder carcinoma cells.

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p120ctn表达改变在膀胱癌中的预后意义

目的研究p120ctn在膀胱肿瘤中表达和定位的变化频率及其与临床预后的关系，探讨p120ctn在膀胱癌细胞迁移和侵袭行为中的潜在作用。材料与方法将534例患者的425例浅表性肿瘤标本(Ta, Tis和T1)和305例侵袭性肿瘤标本(T2-T4)组装在10个组织芯片上。对P120ctn免疫染色进行强度和细胞定位评分，并与临床变量和生存分析相关。使用小干扰RNA (siRNA)实现p120ctn的敲低，然后在标准的体外实验中评估迁移和侵袭行为。结果p120 catenin的表达水平与肿瘤病理分期(P < 0.001)、组织学分级(P < 0.001)、是否存在淋巴血管侵犯(P = 0.02)呈负相关，但与淋巴结(LN)受累无关(P = 0.17)。p120ctn的非膜性定位与分期(P < 0.001)、分级(P < 0.001)、淋巴血管浸润(P = 0.04)和ln阳性疾病(P = 0.02)相关。在癌症特异性生存分析中，p120ctn的低表达水平与预后不良有关。使用siRNA敲除p120ctn可显著降低膀胱癌细胞的迁移和侵袭潜力。结论:我们的研究结果表明p120ctn作为膀胱肿瘤的预后因子，在膀胱癌细胞的迁移和侵袭行为中起主要作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BJU International 医学-泌尿学与肾脏学

CiteScore

9.10

自引率

4.40%

发文量

262

审稿时长

1 months

期刊介绍： BJUI is one of the most highly respected medical journals in the world, with a truly international range of published papers and appeal. Every issue gives invaluable practical information in the form of original articles, reviews, comments, surgical education articles, and translational science articles in the field of urology. BJUI employs topical sections, and is in full colour, making it easier to browse or search for something specific.