Epstein-Barr virus infection in sarcomatoid renal cell carcinoma tissues.
OBJECTIVE
To determine whether Epstein-Barr virus (EBV) infection is related to renal cell carcinoma (RCC) tissues.


METHODS
We investigated EBV infection and its genotypes in 73 cases of different types of RCC and 18 of non-neoplastic kidney. EBV infection and its genotypes were determined by EBV-encoded RNAs in situ hybridization (EBER-ISH) and polymerase chain reactions for EBV-encoded nuclear antigen 1 (EBNA-1) and EBNA-3C. The immunophenotype and EBV status of the EBV-infected cells were examined by double-labelling of EBER-ISH and/or immunohistochemistry for lymphoid cell markers, EBV proteins, and CD21.


RESULTS
EBER-ISH signals were detected in five of 73 RCC tissues (6.8%), but in none of 18 non-neoplastic kidneys. Interestingly, EBER-ISH was positive only in five of the 10 sarcomatoid RCCs, and of these, four also showed amplification of EBNA-1. EBV was located exclusively in the tumour-infiltrating B lymphocytes of sarcomatoid RCCs. The genotype of EBV was determined as type 1. A few EBV-infected B cells expressed BZLF1 (an EBV immediate-early gene product) while none expressed EBNA-2 or latent membrane protein 1. This indicates that the B cells are of EBV latency type I, often replicating EBV. EBV infection did not affect the survival rates of patients with sarcomatoid RCC (P = 0.635, Kaplan-Meier analysis, log-rank test).


CONCLUSIONS
EBV is present only in tumour-infiltrating B lymphocytes of sarcomatoid RCCs. The present study suggests that sarcomatoid RCC modulates a function of EBV-specific T cells controlling EBV replication, or stimulates differentiation of memory B cells into plasma cells.
Kim
Kwang Hee
KH
Department of Pathology, Korea University Ansan Hospital, College of Medicine, Korea University, Ansan, Gyeonggi-Do, South Korea.
Han
Eun Mee
EM
Lee
Eung Seok
ES
Park
Hong Seok
HS
Kim
Insun
I
Kim
Young-Sik
YS
D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000235:genetics; D001402:B-Lymphocytes / Q000821:virology; D015415:Biomarkers / Q000032:analysis; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000473:pathology / Q000821:virology*; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000276:immunology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics; D005260:Female; D005838:Genotype; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization; D007680:Kidney Neoplasms / Q000276:immunology / Q000473:pathology / Q000821:virology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000821:virology; D008297:Male; D008875:Middle Aged; D018198:Mixed Tumor, Malignant / Q000276:immunology / Q000473:pathology / Q000821:virology*; D016133:Polymerase Chain Reaction / Q000379:methods; D012367:RNA, Viral / Q000032:analysis*; D017464:Receptors, Complement 3d / Q000032:analysis; D012509:Sarcoma / Q000276:immunology / Q000821:virology; D017735:Virus Latency
D000956:Antigens, Viral; D015415:Biomarkers; C498774:EBNA-3C, epstein-barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D012367:RNA, Viral; D017464:Receptors, Complement 3d; C417029:EBV-encoded nuclear antigen 1