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通过对福尔马林固定的经尿道切除术活检组织进行ERBB2、ESR1、PGR和MKI67的逆转录定量聚合酶链反应(RT-qPCR)检测,评估分子亚型在非肌层浸润性膀胱癌(NMIBC)中的预测价值。

Predictive value of molecular subtyping in NMIBC by RT-qPCR of ERBB2, ESR1, PGR and MKI67 from formalin fixed TUR biopsies.

作者信息

Breyer Johannes, Wirtz Ralph Markus, Otto Wolfgang, Laible Mark, Schlombs Kornelia, Erben Philipp, Kriegmair Maximilian Christian, Stoehr Robert, Eidt Sebastian, Denzinger Stefan, Burger Maximilian, Hartmann Arndt

机构信息

Department of Urology, University of Regensburg, Regensburg, Germany.

STRATIFYER Molecular Pathology GmbH, Cologne, Germany.

出版信息

Oncotarget. 2017 Jun 28;8(40):67684-67695. doi: 10.18632/oncotarget.18804. eCollection 2017 Sep 15.

Abstract

Expression of ESR1, PGR, HER2 and Ki67 is important for risk stratification and therapy in breast cancer. Hormone receptor expression can also be found in MIBC, reflecting luminal and basal subtypes of breast cancer. Thus the purpose was to investigate on the mRNA expression of the aforementioned markers and their prognostic value in pT1 bladder cancer. Retrospective analysis of clinical data and Formalin-Fixed Paraffin-Embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder was performed. mRNA expression was measured by single step RT-qPCR. Relative gene expression was determined by normalization to two housekeeping genes (CALM2, B2M) using the 40-ΔΔCT method. Correlation of mRNA expression with outcome was assessed using Kaplan-Meier analysis and multivariate Cox regression analysis. From overall 302 patients, 255 samples could be analyzed with valid measurements. Subtype distribution was Luminal-A in 11.4%, Luminal-B in 38.8%, triple negative in 36.9% and ERBB2 in 12.9%, respectively. Kaplan-Meier analysis revealed molecular subtyping being statistical significant for RFS (p=0.0408) and PFS (p=0.0039). Luminal-A patients did have the best RFS and PFS. Multivariate analysis revealed molecular subtyping to be significant for PFS (L-R Chi of 11.89, p=0.0078). Elevated expression of HER2 was statistically significant for PFS (p=0.0025) and discriminated among G3 tumors a high risk group (60% PFS) from a low risk risk group (90% PFS) after 5 year follow-up (p<0.001). Expression of ESR1, PGR and HER2 has predictive value in stage pT1 NMIBC and reveals potential therapeutic targets.

摘要

雌激素受体1(ESR1)、孕激素受体(PGR)、人表皮生长因子受体2(HER2)和Ki67的表达对乳腺癌的风险分层和治疗具有重要意义。在肌层浸润性膀胱癌(MIBC)中也可发现激素受体表达,这反映了乳腺癌的管腔型和基底型亚型。因此,本研究旨在探讨上述标志物在pT1期膀胱癌中的mRNA表达及其预后价值。对接受经尿道膀胱肿瘤切除术的pT1期非肌层浸润性膀胱癌(NMIBC)患者的临床资料和福尔马林固定石蜡包埋组织(FFPE)进行回顾性分析。采用一步法逆转录定量聚合酶链反应(RT-qPCR)检测mRNA表达。使用40-ΔΔCT法,通过将两个管家基因(钙调蛋白2(CALM2)、β2微球蛋白(B2M))标准化来确定相对基因表达。使用Kaplan-Meier分析和多变量Cox回归分析评估mRNA表达与预后的相关性。在总共302例患者中,255份样本可进行有效测量分析。亚型分布分别为管腔A型占11.4%、管腔B型占38.8%、三阴性占36.9%以及ERBB2型占12.9%。Kaplan-Meier分析显示分子亚型对无复发生存期(RFS,p = 0.0408)和无进展生存期(PFS,p = 0.0039)具有统计学意义。管腔A型患者的RFS和PFS最佳。多变量分析显示分子亚型对PFS具有显著意义(似然比卡方值为11.89,p = 0.0078)。HER2表达升高对PFS具有统计学意义(p = 0.0025),并且在5年随访后,在G3肿瘤中区分出高风险组(PFS为60%)和低风险组(PFS为90%)(p < 0.001)。ESR1、PGR和HER2的表达在pT1期NMIBC中具有预测价值,并揭示了潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e9d/5620203/4d7f6eb8a3ae/oncotarget-08-67684-g001.jpg

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