Breyer Johannes, Otto Wolfgang, Wirtz Ralph M, Wullich Bernd, Keck Bastian, Erben Philipp, Kriegmair Maximilian C, Stoehr Robert, Eckstein Markus, Laible Mark, Schlombs Kornelia, Eidt Sebastian, Denzinger Stefan, Burger Maximilian, Hartmann Arndt
Department of Urology, University of Regensburg, Regensburg, Germany.
Urol Int. 2017;98(3):282-289. doi: 10.1159/000453670. Epub 2016 Dec 17.
Background/Aims/Objectives: It is difficult to identify patients with a non-muscle-invasive bladder cancer (NMIBC) at stage pT1 with concomitant carcinoma in situ (Cis) who will benefit from an early cystectomy.
We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues of patients with NMIBC. Messenger ribonucleic acid (mRNA) expression of progesterone receptor (PGR), estrogen receptor (ESR1), ERBB2, and marker of proliferation Ki-67 (MKI67) was measured by single-step reverse transcription quantitative real-time polymerase chain reaction using RNA-specific TaqMan assays. Relative gene expression was determined by the normalization of 2 reference genes (CALM2, B2M) using the 40 ΔΔCT method and relative gene expression was correlated to the histopathological stage and oncological outcome.
Of 302 patients with pT1 NMIBC in the initial transurethral resection of the bladder, 65 had a concomitant Cis. Elevated ERBB2 expression (>40.1) significantly correlated with progress in patients with and without concomitant Cis (p = 0.020 and p = 0.049, respectively). For the subgroup of pT1 with concomitant Cis, elevated ERBB2 expression significantly discriminated between a high-risk group of 55% progression-free survival (PFS) and a low-risk group of 90% PFS after a 5-year follow-up (p = 0.020). Cox-regression analysis revealed ERBB2 expression as the only independent prognostic factor for PFS (p = 0.0037).
High mRNA expression of ERBB2 can identify patients with pT1 NMIBC with concomitant Cis, who have a high risk of progression and might benefit from an early cystectomy.
背景/目的:难以识别伴有原位癌(Cis)的pT1期非肌层浸润性膀胱癌(NMIBC)患者中哪些会从早期膀胱切除术中获益。
我们回顾性分析了NMIBC患者的临床数据和福尔马林固定石蜡包埋组织。使用RNA特异性TaqMan分析通过单步逆转录定量实时聚合酶链反应测量孕激素受体(PGR)、雌激素受体(ESR1)、ERBB2和增殖标志物Ki-67(MKI67)的信使核糖核酸(mRNA)表达。使用40ΔΔCT方法通过2个参考基因(CALM2、B2M)的标准化确定相对基因表达,并将相对基因表达与组织病理学分期和肿瘤学结果相关联。
在最初经尿道膀胱切除术中的302例pT1期NMIBC患者中,65例伴有Cis。ERBB2表达升高(>40.1)与伴有和不伴有Cis的患者进展显著相关(分别为p = 0.020和p = 0.049)。对于伴有Cis的pT1亚组,ERBB2表达升高在5年随访后显著区分了无进展生存期(PFS)为55%的高危组和PFS为90%的低危组(p = 0.020)。Cox回归分析显示ERBB2表达是PFS的唯一独立预后因素(p = 0.0037)。
ERBB2的高mRNA表达可识别伴有Cis的pT1期NMIBC患者,这些患者进展风险高,可能从早期膀胱切除术中获益。