Epstein-Barr virus infection in sarcomatoid renal cell carcinoma tissues

BJU Int. 2005 Sep;96(4):547-52. doi: 10.1111/j.1464-410X.2005.05682.x.

Abstract

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

Materials and 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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Viral / genetics
  • B-Lymphocytes / virology
  • Biomarkers / analysis
  • Carcinoma, Renal Cell / immunology
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / virology*
  • Epstein-Barr Virus Infections / complications*
  • Epstein-Barr Virus Infections / immunology
  • Epstein-Barr Virus Nuclear Antigens / genetics
  • Female
  • Genotype
  • Herpesvirus 4, Human / genetics*
  • Humans
  • Immunohistochemistry / methods
  • In Situ Hybridization
  • Kidney Neoplasms / immunology
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / virology*
  • Lymphocytes, Tumor-Infiltrating / virology
  • Male
  • Middle Aged
  • Mixed Tumor, Malignant / immunology
  • Mixed Tumor, Malignant / pathology
  • Mixed Tumor, Malignant / virology*
  • Polymerase Chain Reaction / methods
  • RNA, Viral / analysis*
  • Receptors, Complement 3d / analysis
  • Sarcoma / immunology
  • Sarcoma / virology
  • Virus Latency

Substances

  • Antigens, Viral
  • Biomarkers
  • EBNA-3C, epstein-barr virus
  • Epstein-Barr Virus Nuclear Antigens
  • RNA, Viral
  • Receptors, Complement 3d
  • EBV-encoded nuclear antigen 1