Detection of Epstein-Barr virus in rapidly growing fibroadenomas of the breast in immunosuppressed hosts

Abstract

Fibroadenomas are the most common benign tumors of the female breast and are associated with a slight increase in the risk of subsequent breast cancer. Multiple fibroadenomas have been described in patients after renal transplantation and are thought to be secondary to drug-related growth stimulation. Epstein-Barr virus (EBV) has been detected in many neoplasms, including breast cancer. We set out to investigate whether EBV plays a role in the development of rapidly growing fibroadenomas in immunocompromised patients. We studied 19 fibroadenomas and one invasive ductal carcinoma that developed after organ transplantation or treatment for lupus erythematosus. As a control group we included 11 fibroadenomas from non-immunocompromised patients. DNA was amplified using polymerase chain reaction (PCR) of the EBV-encoded small RNA (EBER-2) DNA sequence. EBV latent membrane protein 1 (LMP-1) transcripts were amplified using reverse transcription (RT) PCR. Immunohistochemical (IHC) staining for LMP-1 protein was performed. A total of 9 out of 20 tumors (45%) were concordantly positive by PCR and IHC. IHC stained exclusively the epithelial cells. All the fibroadenomas in non-immunocompromised patients were negative for LMP-1 (Fisher's exact test P =.0006). These data suggest that EBV is associated with fibroadenomas in this immunosuppressed population and that the infection is specifically localized to epithelial cells. This is the first study suggesting a role for EBV in the pathogenesis of fibroadenomas.