Epstein-Barr virus in epithelial cell tumors: a breast cancer study.

The human herpes virus Epstein-Barr (EBV) is clearly associated with African Burkitt's lymphoma and the undifferentiated from of nasopharyngeal carcinoma, although its role in oncogenesis is still poorly defined. Recently EBV has been implicated in other types of lymphomas, as well as in some nonlymphomatous neoplastic processes. Its possible association with human breast cancer has been investigated here. DNA from 91 cases of breast carcinoma and blood samples from the same patients were amplified with the PCR over a region in the EBV BamHIW major repeat sequence following a single-step amplification protocol. Nineteen samples (21%) were found to be positive; 10 samples of blood (only 3 of them from patients with EBV-positive tumors) were found by the adopted protocol to contain EBV DNA. Another series of PCR amplifications using primers covering a unique (nonreiterated) fragment in BamHIC encoding the EBERs (two short nonpolyadenylated RNAs generally highly expressed in cells latently infected with EBV) confirmed these findings. A good correlation between the two sets of experiments was observed, and only five differences in results were obtained on samples tested. In situ hybridization was carried out using BamHIW biotinylated DNA probes or EBER-1 digoxigenin-labeled riboprobes with the aim of confirming as well as localizing the signal to the epithelial cell. Twelve sections (63%) among the PCR-positive samples were found positive by in situ hybridization with the DNA probe, and six (31.5%) sections were found with the RNA probe. Twenty-one samples from benign breast tumors or normal breast tissue were used as controls for PCR amplification in this study, none of which was found positive. This is the first known report showing positive results for EBV in breast cancer. No statistical association was found in these studies between the presence of EBV and the histological type of the tumor, however. Its role therefore remains for the moment unknown, as well as does the significance of the association of EBV with only a subset of the cases.

[1]  J. Najarian,et al.  Clinical spectrum of lymphoproliferative disorders in renal transplant recipients and evidence for the role of Epstein-Barr virus. , 1981, Cancer research.

[2]  I. Ellis,et al.  Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. , 2002, Histopathology.

[3]  B. Griffin,et al.  Clustered repeat sequences in the genome of Epstein Barr virus. , 1983, Nucleic acids research.

[4]  F. Rilke,et al.  Primary Non‐Hodgkin's lymphomas of the female breast , 1992, Cancer.

[5]  D. Wright,et al.  Burkitt's tumour presenting as bilateral swelling of the breast in women of child‐bearing age , 1967, The British journal of surgery.

[6]  A. Sasco,et al.  Review article: Epidemiology of male breast cancer. A meta‐analysis of published case‐control studies and discussion of selected aetiological factors , 1993, International journal of cancer.

[7]  L. Labrecque.  In situ hybridisation of EBV DNA-DNA hybrids using wet heat in polypropylene containers. , 1992, Journal of clinical pathology.

[8]  John E. Bennett,et al.  Principles and practice of infectious diseases. Vols 1 and 2. , 1979 .

[9]  G. Srivastava,et al.  Epstein-Barr virus DNA in nasopharyngeal carcinomas from Chinese patients in Hong Kong. , 1992, Journal of clinical pathology.

[10]  B. Griffin,et al.  Immortalization of monkey epithelial cells by specific fragments of Epstein–Barr virus DNA , 1984, Nature.

[11]  J. Steitz,et al.  Two small RNAs encoded by Epstein-Barr virus and complexed with protein are precipitated by antibodies from patients with systemic lupus erythematosus. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[12]  L. Young,et al.  Identification of a human epithelial cell surface protein sharing an epitope with the C3d/epstein‐barr virus receptor molecule of B lymphocytes , 1989, International journal of cancer.

[13]  R. Curran.  Colour Atlas of Histopathology , 1972 .

[14]  K. Chan,et al.  Epstein‐barr virus carriage by nasopharyngeal carcinoma in situ , 1993, International journal of cancer.

[15]  D. Shibata,et al.  Epstein-Barr virus-associated gastric adenocarcinoma. , 1992, The American journal of pathology.

[16]  M. Hitt,et al.  Establishment of immortalized primate epithelial cells with sub‐genomic EBV DNA , 1990, International journal of cancer.

[17]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[18]  S. Hoisington,et al.  Uterine cervical lymphoepithelial-like carcinoma. Absence of Epstein-Barr virus genomes. , 1993, American journal of clinical pathology.

[19]  P. Volberding,et al.  Non-Hodgkin's lymphoma in 90 homosexual men. Relation to generalized lymphadenopathy and the acquired immunodeficiency syndrome. , 1984, The New England journal of medicine.

[20]  I. Ernberg,et al.  EBV gene expression in an NPC‐related tumour. , 1989, The EMBO journal.

[21]  S. Pittaluga,et al.  Clonal Epstein-Barr virus in lymphoepithelioma-like carcinoma of the stomach: demonstration of viral genome by in situ hybridization and Southern blot analysis. , 1992, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[22]  P. Carbone,et al.  Lymphoma of the Breast , 1981, Annals of surgery.

[23]  S. Pettit,et al.  Endogenous avidin-binding activity in human lymphoid tissue. , 1984, Journal of clinical pathology.

[24]  R. Warnke,et al.  Epstein-Barr viral DNA in tissues of Hodgkin's disease. , 1987, The American journal of pathology.

[25]  L. Bégin,et al.  Epstein‐barr virus related lymphoepithelioma‐like carcinoma of lung , 1987, Journal of surgical oncology.

[26]  L. Young,et al.  Human epithelial cell expression of an Epstein-Barr virus receptor. , 1987, The Journal of general virology.

[27]  M. Epstein,et al.  VIRUS PARTICLES IN CULTURED LYMPHOBLASTS FROM BURKITT'S LYMPHOMA. , 1964, Lancet.