Epstein-Barr virus-encoded small RNAs in idiopathic orbital inflammatory pseudotumor tissues: a comparative case series

AIM： To investigate the positive rate and types of cells that express Epstein-Barr virus-encoded small RNAs （EBERs） and to determine the distribution of EBER-expressing cells in idiopathic orbital inflammatory pseudotumor （IOIP） tissues. METHODS： We retrospectively examined 40 archived paraffin specimens from two teaching hospitals in Southern China between January 2007 and January 2015 that were pathologically determined to exhibit IOIP. Eleven concurrent paraffin specimens of thyroid-associated ophthalmopathy （TAO） composed the control group. In situ hybridization was performed to detect EBERs. Immunohistochemistry was employed to detect CD3, CD20, Vimentin, and smooth muscle actin （SMA）, and the positive rate, types of positive cells, and distribution and location of EBERs were evaluated. RESULTS： The positive expression rate of EBERs was 47.5% （19/40） in the IOIP group, which was significantly higher than that in the TAO group [0 （0/11）, P=-0.011]. in the IOIP group, the lymphocyte infiltrative subtype, fibrotic subtype, and mixed subtype exhibited EBER-positive rates of 57.1% （12121）, 12.5% （118）, and 54.5% （6/11）, respectively, and no significant differences were found between these subtypes （P=0.085）. Positive signals of EBERs were mainly present in medium-small lymphocytes between or around follicles and in the nuclei of activated immunoblasts （14/19）. CONCLUSION： The positive rate, types, and distribution of EBER-expressing cells in IOIP have been documented.These findings are conducive for a better understanding of the underlying mechanisms of Epstein-Barr virus infection in IOIP pathogenesis.

Epstein-Barr virus-encoded RNAs as a survival predictor in nasopharyngeal carcinoma

Background Epstein-Barr virus （EBV） infection is one of the most important factors of nasopharyngeal carcinoma （NPC）endemic areas.Transcription of EBV-encoded non-polyadenylated RNAs （EBERs） are presented in most of NPC tumors.Exploring EBERs as a prognostic marker for NPC might further be informative about the biology and the progression of the disease.The aim of this study was to analyze the role of EBV latency in the clinical management of nasopharyngeal carcinoma （NPC）,by detecting EBERs.Methods RNA in situ hybridization （ISH） for detecting EBERs was carried out on 908 NPC tumor tissues.Overall survival （OS） curves were analyzed with the Kaplan-Meier method and the Cox proportional-hazards regression models.Results The median follow-up time was 70 months （1-120 months）.Eight hundred and sixteen （89.9％） from a total of 908 consecutive NPC cases were found to be EBV-EBER positive.EBER-ISH staining revealed nuclear localization in NPC cells.In the Kaplan-Meier analysis for OS,high EBER expression levels in NPC patients were statistically significant positive prognostic factors for survival （log-rank,P=0.022）,especially in adults aged 17-40 years （P=0.023） and in those with advanced stage disease （log-rank,P=0.002）.Cox proportional-hazards regression model analysis showed that the EBER expression level was an independent risk factor for OS （hazard ratio 0.724,P=0.005）.Conclusions EBERs were frequently detected in NPC tumor tissues,and high-level EBER expression correlated with good prognosis in NPC patients,especially in adult patients and in those with advanced stage disease.EBER may serve as a potential prognostic predictor in NPC.

Heterochronic triple primary malignancies with Epstein-Barr virus infection and tumor protein 53 gene mutation:A case report and review of literature

BACKGROUND The diagnosis and etiology of multiple primary malignant neoplasms(MPMNs)are difficult to establish.Here,we report a case of heterochronic triple primary malignancies with gastric cancer,nasopharyngeal squamous cell cancer,and then rectal cancer.CASE SUMMARY The patient was first diagnosed with gastric cancer at the age of 33 in 2014 and underwent distal gastrectomy and gastrojejunostomy and six cycles of adjuvant chemotherapy.Three years later,he was diagnosed with nasopharyngeal cancer and treated with radical chemoradiotherapy in 2017.Recently,a mass in the middle of the rectum was resected and reported as ulcerative,moderately to poorly differentiated adenocarcinoma.Research on the etiology of MPMNs showed that Epstein-Barr virus(EBV)infection may be the cause of gastric cancer and nasopharyngeal squamous cell cancer since these two primary lesions were positive for transcripts of EBV-encoded ribonucleic acid using an in situ hybridization EBV-encoded ribonucleic acid probe in formalin-fixed,paraffinembedded tissue.The cause of rectal cancer may be due to a somatic mutation of tumor protein 53 gene in exon 8(c.844C>T,p.Arg282Trp)through highthroughput sequencing for the rectal cancer.Appropriate standard therapy for each primary cancer was administered,and the patient has no evidence of cancer disease to date.CONCLUSION To our knowledge,this is the first report on heterochronic triple primary malignancies whose cause may be associated with EBV infection and tumor protein 53 genetic mutations.The etiological research may not only elucidate the cause of MPMN but also has implications in clinical management.