Systematic analysis of human oncogenic viruses in colon cancer revealed EBV latency in lymphoid infiltrates

Abstract

BackgroundEnvironmental factors may play a role in colon cancer. In this view, several studies investigated tumor samples for the presence of various viral DNA with conflicting results.FindingsWe undertook a systematic DNA analysis of 44 consecutive, prospectively collected primary tumor samples by real time and qualitative PCR for viruses of known or potential oncogenic role in humans, including polyomavirus (JCV, BKV, Merkel cell polyomavirus), HPV, HTLV, HHV-8 and EBV. Negative controls consisted of surgical resection margins. No evidence of genomic DNA fragments from tested virus were detected, except for EBV, which was found in a significant portion of tumors (23/44, 52%). Real-time PCR showed that EBV DNA was present at a highly variable content (median 258 copies in 105 cells, range 15–4837). Presence of EBV DNA had a trend to be associated with high lymphocyte infiltration (p = 0.06, χ2 test), and in situ hybridization with EBER1-2 probes revealed latency in a fraction of these lymphoid cells, with just a few scattered plasma cells positive for BZLF-1, an immediate early protein expressed during lytic replication. LMP-1 expression was undetectable by immunohistochemistry.ConclusionsThese results argue against a significant involvement of the tested oncogenic viruses in established colon cancer.

BK polyomavirus association with colorectal cancer development

“…The PCR and IHC techniques employed in the current study failed to detect genetic material and protein deriving from the virus under investigation in colorectal carcinoma and control tissues. Our data are consistent with the findings of four other research teams who found no evidence of BKV DNA in a large range of colorectal cancer, adenoma, and normal mucosa samples (Militello et al, 2009;Campello et al, 2010;Fiorina et al, 2014;Ripple et al, 2014). Such contradictions may be explained by false-positive results due to contamination during experimental procedures, the sensitivity of the protocols used, population diversity and sample size variation, and BKV incidence in the geographical area of study.…”

Epstein–Barr virus and its association with Fascin expression in colorectal cancers in the Syrian population: A tissue microarray study

“…More importantly, we were able to show that E6/E7 onco-proteins of high-risk HPV type 16 convert non-invasive and non-metastatic human cancer cells into invasive and metastatic ones. 27 Regarding the presence of EBV in CRC worldwide, several recent investigations reported that 20-50% of these cancer cases are positive for EBV [28][29][30][31][32] ; however, a small number of studies were unable to detect EBV in colorectal carcinomas but in their infiltrated lymphomas. 33,34 Meanwhile, it is important to emphasize that the presence of EBV in the Middle East region is limited to 2 conflicting studies from Iran, as Tafvizi et al, 32 revealed that 38% (19/50) of human CRC cases are positive for EBV in the Iranian population; however, the second study was unable to detect the presence of EBV in only 15 CRC samples.…”

CpG Island Methylator Phenotype-High Colorectal Cancers and Their Prognostic Implications and Relationships with the Serrated Neoplasia Pathway

“…For CRCs, EBV infection is detected in 19% to 52% of CRC tissue specimens by polymerase chain reaction (PCR) 27,28. However, in situ hybridization analyses for the detection of EBER1-2 RNAs demonstrated EBVs in infiltrating nonneoplastic lymphoid cells but not in tumor cells, which contrasts with EBV-positive gastric cancers in which EBV in situ hybridization exhibit EBVs in nearly all of the tumor epithelial cells 26,27. Regardless of whether EBV is present in tumor cells or not, there is no relationship between the presence of EBV in cancer tissue specimens and CIMP 28.…”