The prevalence of EBV and CMV DNA in epithelial ovarian cancer

Abstract

Background The underlying cause of epithelial ovarian cancer (EOC) is unknown. It has been theorized that infectious agents could contribute to ovarian tumorigenesis. Objective To investigate the potential role of oncogenic viral infection in EOC, we examined the prevalence of Epstein-Barr Virus (EBV) DNA and cytomegalovirus (CMV) DNA in EOC tissue samples. Methods Formalin-fixed, paraffin-imbedded (FFPE) tumor tissue samples from 198 patients included in the Danish Pelvic Mass Study were studied: 163 with serous adenocarcinomas, 15 with endometrioid adenocarcinomas, 11 with mucinous adenocarcinomas, and nine with clear-cell carcinomas. For controls in the EBV analysis, we used 176 tissue samples from patients diagnosed with benign mucinous cystadenomas. EBV and CMV genotyping was performed by real-time polymerase chain reaction with CMV and EBV CE-IVD approved kits. In-situ hybridization (ISH) was performed on the EBV positive samples. Results Sufficient DNA material was obtained in 191 and 174 tissue samples from cases and controls, respectively. Ten of 191 case samples (5.2%) and one of 174 control samples (0.5%) were positive for EBV DNA ( P value = 0.011). CMV DNA was detected in only one case sample (0.5%). ISH confirmed that three of the samples were of stromal origin, while the remaining seven tested negative for EBV. Conclusions This study is the first to demonstrate a higher prevalence of EBV DNA in tissue samples from patients with EOC than in a benign control group. However, the cellular origin of seven of the samples could not be determined by ISH analysis. Our study did not support an association between CMV and EOC. Electronic supplementary material The online version of this article (10.1186/s13027-019-0223-z) contains supplementary material, which is available to authorized users.

Factors in Oncogenesis: Viral Infections in Ovarian Cancer

“…The results show the presence of low amounts of CMV DNA in 50%-75% of tumor tissue samples obtained from women with EOC, while low protein expression or expression at different levels was found in most tissue sections, including those from patients with serous EOC [65,[71][72][73]. In contrast, another study did not support any association between CMV and EOC [74]. It has been recently found that almost two-thirds of EOC patients demonstrated coinfection with both CMV and HPV16 in the pathological samples [71].…”

“…It was suggested that tumor heterogeneity, the uneven distribution of infected cells, and differences in the methodological approaches might be a probable reason for no prevalence of CMV in ovarian tumor tissues despite involving a large sample-size study. Higher prevalence of EBV DNA was noted in patients with EOC, as compared to a benign control group [74]. The incongruent findings in the microbiome in OC could be due to the possibility that the involved pathogen was not present at the time point at which OC was diagnosed [86].…”

“…Approximately 50% of ovarian cancers in the Indian population have been shown to be positive for CMV DNA, of which 80% were invasive and 20% were borderline tumors [65]. In contrast, no association was observed between CMV and OC in the Danish population [74]. It was suggested that tumor heterogeneity, the uneven distribution of infected cells, and differences in the methodological approaches might be a probable reason for no prevalence of CMV in ovarian tumor tissues despite involving a large sample-size study.…”

“…EBV appears to play a direct oncogenic role through genome-wide alteration of promoter methylation and expression of miRNA and genes involved in cell motility and transformation pathways [165,166]. EBV DNA has been detected in approximately 5%-7% of EOC tissue samples [74,76], while no DNA virus transcripts were detected in ovarian serous cystadenocarcinoma [75]. Moreover, no association between EOC and EBV antibody levels has been found [167].…”

Detection of Human Cytomegalovirus in Patients with Epithelial Ovarian Cancer and its Impacts on Survival

“…reported that HCMV proteins and nucleic acids are frequently detected at different levels in high grade serous ovarian carcinoma, and shorter median overall survival was shown in patients with positive HCMV-IE and pp65. However, Ingerslev et al [13]examined the prevalence of Epstein-Barr Virus (EBV) DNA and HCMV DNA in EOC tissue samples, HCMV DNA was detected in only one case sample (0.5%), showing no association between HCMV and EOC.…”