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

Epstein-Barr virus (EBV) could be detected in bladder cancer. In our paper, we showed that DNA of EBV could be detected more in the high grade urothelial carcinoma. In superficial bladder cancer, although high grade tumour associated with higher EBV titers, the recurrence free survival was not compromised by high EBV DNA load. 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 mu L) 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.