RESUMEN
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.
Asunto(s)
Carcinoma de Células Renales/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4/genética , Neoplasias Renales/virología , Tumor Mixto Maligno/virología , ARN Viral/análisis , Adulto , Anciano , Antígenos Virales/genética , Linfocitos B/virología , Biomarcadores/análisis , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/patología , Infecciones por Virus de Epstein-Barr/inmunología , Antígenos Nucleares del Virus de Epstein-Barr/genética , Femenino , Genotipo , Humanos , Inmunohistoquímica/métodos , Hibridación in Situ , Neoplasias Renales/inmunología , Neoplasias Renales/patología , Linfocitos Infiltrantes de Tumor/virología , Masculino , Persona de Mediana Edad , Tumor Mixto Maligno/inmunología , Tumor Mixto Maligno/patología , Reacción en Cadena de la Polimerasa/métodos , Receptores de Complemento 3d/análisis , Sarcoma/inmunología , Sarcoma/virología , Latencia del VirusRESUMEN
Tumor cells from a malignant mixed tumor of the lacrimal gland were maintained in tissue culture for more than 55 generations. Comparative immunohistochemical analysis was performed on whole tumor sections and on the tumor cell culture to define the origin of the cells in culture. The cultured cells expressed cytokeratin, smooth-muscle actin, S-100 protein, and vimentin and were negative for glial fibrillary acidic protein. Tumor sections expressed cytokeratin but were negative for muscle-specific actin, vimentin, and glial fibrillary acidic protein. Through tissue culture studies of salivary gland epithelial neoplasias, which are very similar to lacrimal gland epithelial neoplasias, pluripotential stem cells have been identified. Similar tissue culture analysis of lacrimal gland epithelial neoplasms can be a valuable tool for studying the origin of these uncommon tumors.