Original article
Evaluation of the presence of Epstein-Barr virus (EBV) in Iranian patients with thyroid papillary carcinoma

https://doi.org/10.1016/j.prp.2017.01.020Get rights and content

Abstract

Background and purpose

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. EBV is one of the most important viruses related to different types of malignancies. This study investigated the relationship between EBV and papillary thyroid carcinoma.

Material and methods

In this study the presence of Epstein-Barr Nuclear Antigen 1 (EBNA1) gene in papillary thyroid carcinoma tissues were examined by nested-PCR method. Paraffin-embedded tissues (N = 41) blocks of thyroid cancer were used. DNA was extracted from all samples and then samples were evaluated for the presence of EBV gene.

Results

In 41 samples, EBNA1 was detected in 65.8% of patients with papillary thyroid carcinoma which was significantly higher in younger ages.

Conclusion

The significant presence of EBV genome in papillary thyroid carcinoma suggests that this virus may play a role in this cancer especially in younger ages. As a result, monitoring of patients with EBV latent infection for PTC can be very important.

Introduction

Studies show that approximately 1–2% of overall cancers occur in thyroid [1]. In Iran, 1.8% of overall cancers and 76.1% of endocrine tumor cancers are types of thyroid cancer [2]. Papillary thyroid carcinoma (PTC) is the most common thyroid cancer and its prevalence in women is twice that of men which occurs in 30–50 years. The disease is attributed to several genetically and environmental factors. Most recently viral agents have also been considered as one of its causes. The main viral agent which infect nasopharyngeal region is Epstein-Barr virus (EBV) which might be associated with development of cancer in this site. EBV which is named HHV4 belongs to Herpesviridae family causes infectious mononucleosis. The virus is associated with Hodgkin’s lymphoma, Burkitt’s lymphoma, nasopharyngeal carcinoma, lung cancer and gastric cancer [3]. More than 90% of adult people in the world are contaminated with EBV. The virus is transmitted through saliva, during acute infection which infects the stratified squamous epithelium of the oropharynx [4]. It is known that EBV targets different functions of cells and by creating instability in the genome cause cancer [5]. The viral genome consists of a double-stranded DNA with 85 genes including Latent Membrane Protein (LMP1, LMP2A. LMP2B) and Epstein-Barr Nuclear Antigen (EBNA1 and EBNA2B) genes involved in nasopharyngeal carcinoma [6]. LMP1 is one of the most important nasopharyngeal carcinoma oncogenes. Studies show LMP1+ cells have more motility which increase the metastatic potential of tumor, also it can suppress immune responses through effects on IL-6/8, TNFRs(as CD40), NF-kB, JAK/STAT pathway and etc. [7]. EBNA1 attaches the EBV genomes into the cell’s genome [8]. EBV increases the oncogenes expression as P53, C-Met and bcl-2 [9]. Therefore in this study, the presence of EBNA1 gene in papillary thyroid carcinoma has been studied.

Section snippets

Patients

In this retrospective study, forty one paraffin-embedded tissue blocks from all patients with papillary thyroid cancer who underwent thyroid surgery at Imam Khomeini Hospital (Tehran, Iran) between 2012 and 2014 were collected and pathology report information were evaluated. Patients were included in the study whose diagnoses were based on the final pathology report after thyroidectomy. Metastatic focus of PTC in other tissues (for example lymphe node) were not used. No other inclusion and

Baseline characteristics

The baseline characteristics of papillary thyroid carcinoma patients are shown in Table 2. The study consists of 41 patients including 9 (22%) males and 32(78%) females. The age was divided into three groups: <40, 40–50 and >50 years old which the most of patients 17(41.4%) were in >50 groups. According to the type of papillary thyroid carcinoma, 35(85.4%) of patients were conventional variant type. In terms of the disease stage, 30(73.2%) were in stage one. Tumor was encapsulated in 19(46.3%)

Discussion

This study showed that among our patients with papillary thyroid carcinoma large number of samples were positive for presence of EBV EBNA1 gene and also frequency of the virus was higher in younger age which suggests that this virus may play a role in PTC development in younger people.

As mentioned, EBV has been considered as one of the most important factors causing a variety of cancers in lymphoid and epithelioid tissues such as papillary thyroid carcinoma in recent years [10]. Papillary

Conflict of interest

Authors declare that they have no financial interests related to the material in the manuscript.

Funding

This project was supported by Endocrinology and Metabolism Clinical Sciences Institute (Tehran University of Medical Science).

Authors’ contributions

MMA and FR proposed the concept of study. FN assisted in sample collection and confirmation of diagnosis. MH did the molecular analysis. MMA and MH analyzed the results. Initial draft of the manuscript was written by MH, which was reviewed and edited by FR, MMA, FN and SAMA. All authors read and approved the final manuscript.

Acknowledgements

We wish to thank the staff of the department of pathology of Imam Khomeini Hospital and Endocrinology and Metabolism Clinical Sciences Institute.

References (18)

There are more references available in the full text version of this article.
1

Kerman University of Medical Sciences, End of 22 Bahman Blv, Kerman, Iran.

2

Imam Khomeini Hospital, End of Keshavarz Blv, Tehran, Iran.

3

Shariati Hospital, North Kargar St., Tehran, Iran.

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