- Short Report
- Open Access
Systematic analysis of human oncogenic viruses in colon cancer revealed EBV latency in lymphoid infiltrates
© Fiorina et al.; licensee BioMed Central Ltd. 2014
- Received: 30 December 2013
- Accepted: 28 April 2014
- Published: 3 June 2014
Environmental 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.
We 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, χ 2 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.
These results argue against a significant involvement of the tested oncogenic viruses in established colon cancer.
- Colon cancer
- Oncogenic viruses
It is estimated that 16-18% of the global cancer burden can be associated with oncogenic viruses [1, 2]. The DNA viruses of recognized pathogenic role in humans include HCV, HBV, HPV, HHV-8, MCPyV and EBV, while the role of polyomaviruses JCV and BKV is controversial [1, 3]. Colon cancer is a leading cause of cancer-related death and morbidity in western countries. The pathogenesis of this cancer is highly complex and it involves sequential genetic and epigenetic mechanisms [4, 5]. A possible contribution of environmental agents, including bacteria and viruses, is also considered [6, 7]. However, the search for a pathogenic agent generated conflicting results, possibly related to technical reasons or other unknown factors .
Clinical and pathological features of the colon cancer cases analysed for potential oncogenic viruses
Colon cancer (n = 44)
No. of cases
Median of age = 75 years (range 46–84)
≤ 65 years
≥ 65 years
Sigmoid - Rectal
< 65 years
In conclusion, we performed a PCR-based systematic analysis for potential oncogenic viruses in clinically established colon cancer and EBV was the only one detected. The viral infection was restricted to latency in the lymphoid infiltrate, in line with the few reports that used in situ hybridization with EBER probes [19, 20], while we noted an association with high lymphocyte infiltration, a well-recognized favorable prognostic parameter. EBV positivity in lymphoid infiltrates may occasionally be extensive (Figure 1), much higher than expected on the numbers of circulating EBV positive memory B-lymphocytes in normal individuals, and it might be of interest to studying this phenomenon in specifically designed studies. In summary, the present analysis does not support a significant involvement of the tested viruses in manifest colon cancer, and suggests that new approaches  capable of detecting known and unknown non-human sequences should be investigated to study the role of infectious agents in colon cancer.
The study was supported by Fondazione IRCCS Policlinico “San Matteo”, Ricerca Corrente to VP and FB. ED is recipient of a fellowship from Anatomic Pathology Section, IRCCS Fondazione Policlinico “San Matteo,” Pavia, Italy; RR is a recipient of a grant (project #580) from the Italian Ministry of Health (5 per Mille) of IRCCS Fondazione Policlinico “San Matteo”, Pavia, Italy.
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