肿瘤组织中 Epstein-Barr 病毒 DNA 载量与非肌肉浸润性尿路上皮癌的低分化状态相关。

Epstein-Barr virus DNA load in tumour tissues correlates with poor differentiation status in non-muscle invasive urothelial carcinomas.

机构信息

Division of Uro-oncology, Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.

出版信息

BJU Int. 2011 Jan;107(1):150-4. doi: 10.1111/j.1464-410X.2010.09474.x. Epub 2010 Aug 24.

DOI:10.1111/j.1464-410X.2010.09474.x

PMID:20735392

Abstract

OBJECTIVE

To detect the correlation between the clinical staging, grading and genomic Epstein-Barr virus (EBV) viral numbers in tumour tissues of urothelial carcinoma patients.

PATIENTS AND METHODS

From June 2004 to May 2008, 60 urothelial carcinoma patients (50 cases of bladder carcinoma and 10 of upper tract urothelial carcinoma (UTUC) were enrolled in the study. Eight patients who underwent transurethral resection of prostate for prostate hyperplasia and two patients receiving nephrectomy for non-function kidney were used as normal controls. The EBV viral copy numbers in genomic DNA were evaluated using a real-time PCR-based study. The BamHI W region of the Namalwa cell line was constructed to the plasmid clone and was used as standard curve for absolute quantitative PCR (Q-PCR).

RESULTS

Epstein-Barr virus DNA was detected in 56% (28/50) and 60% (6/10) of the bladder and UTUC patients, respectively. The EBV DNA could not be detected in the normal control group. By pooling the UTUC and bladder patients in stage Ta,T1, the high copy number in fixed genomic DNA amount (100 ng/20 µL) was correlated with the high grading in stage Ta,T1 urothelial carcinoma (P = 0.014). The overall grading was not statistically associated with EBV copy number (P = 0.25). Although the copy numbers between paired tumour and normal tissues were not statistically different (P= 0.169), there were more copies of EBV in the normal tissues adjacent to the tumours than in those free from urothelial carcinoma. There was no significant difference between recurrence of non-muscle invasive bladder cancer and the presence of EBV (P > 0.05).

CONCLUSIONS

Epstein-Barr virus DNA could be detected in the genome of the urothelial carcinoma specimens. The poor differentiation status was correlated with the high load of the EBV genome in non-muscle invasive urothelial carcinoma. However, recurrence-free survival was not greater in EBV-positive patients than in EBV-negative patients.

摘要

目的

检测膀胱癌和上尿路上皮癌患者肿瘤组织中临床分期、分级和基因组 EBV 病毒数量之间的相关性。

方法

本研究纳入了 60 例尿路上皮癌患者（50 例膀胱癌和 10 例上尿路上皮癌），并于 2004 年 6 月至 2008 年 5 月进行了研究。选取 8 例因前列腺增生行经尿道前列腺切除术的患者和 2 例因无功能肾行肾切除术的患者作为正常对照。使用基于实时 PCR 的研究评估 EBV 病毒基因组 DNA 的拷贝数。使用 Namalwa 细胞系的 BamHI W 区构建质粒克隆，并用作绝对定量 PCR (Q-PCR) 的标准曲线。

结果

膀胱癌和上尿路上皮癌患者的 EBV DNA 检出率分别为 56%（28/50）和 60%（6/10）。正常对照组未检出 EBV DNA。将上尿路上皮癌和膀胱癌患者合并为 Ta、T1 期后，固定基因组 DNA 量（100 ng/20 μL）中的高拷贝数与 Ta、T1 期尿路上皮癌的高分级相关（P = 0.014）。总体分级与 EBV 拷贝数无统计学关联（P = 0.25）。尽管肿瘤组织与正常组织之间的拷贝数无统计学差异（P = 0.169），但肿瘤附近的正常组织中 EBV 的拷贝数更多。非肌层浸润性膀胱癌的复发与 EBV 的存在之间无显著差异（P > 0.05）。