Abstract
BackgroundBreast cancer is a leading cause of death among women worldwide. Increasing evidence implies that human cytomegalovirus (HCMV) infection is associated with several malignancies. We aimed to examine whether HCMV is present in breast cancer and sentinel lymph node (SLN) metastases.Materials and MethodsFormalin-fixed paraffin-embedded tissue specimens from breast cancer and paired sentinel lymph node (SLN) samples were obtained from patients with (n = 35) and without SLN metastasis (n = 38). HCMV immediate early (IE) and late (LA) proteins were detected using a sensitive immunohistochemistry (IHC) technique and HCMV DNA by real-time PCR.ResultsHCMV IE and LA proteins were abundantly expressed in 100% of breast cancer specimens. In SLN specimens, 94% of samples with metastases (n = 34) were positive for HCMV IE and LA proteins, mostly confined to neoplastic cells while some inflammatory cells were HCMV positive in 60% of lymph nodes without metastases (n = 35). The presence of HCMV DNA was confirmed in 12/12 (100%) of breast cancer and 10/11 (91%) SLN specimens from the metastatic group, but was not detected in 5/5 HCMV-negative, SLN-negative specimens. There was no statistically significant association between HCMV infection grades and progesterone receptor, estrogen receptor alpha and Elston grade status.ConclusionsThe role of HCMV in the pathogenesis of breast cancer is unclear. As HCMV proteins were mainly confined to neoplastic cells in primary breast cancer and SLN samples, our observations raise the question whether HCMV contributes to the tumorigenesis of breast cancer and its metastases.
Highlights
Breast cancer is the most common malignancy and a leading cause of cancer death in women worldwide
The presence of human cytomegalovirus (HCMV) DNA was confirmed in 12/12 (100%) of breast cancer and 10/11 (91%) sentinel lymph node (SLN) specimens from the metastatic group, but was not detected in 5/5 HCMV-negative, SLN-negative specimens
As HCMV proteins were mainly confined to neoplastic cells in primary breast cancer and SLN samples, our observations raise the question whether HCMV contributes to the tumorigenesis of breast cancer and its metastases
Summary
Breast cancer is the most common malignancy and a leading cause of cancer death in women worldwide (reviewed in [1]). HCMV and human herpesvirus-8 (HHV-8) positivity in breast cancer was associated with lower relapse-free time and overall survival [5]. HCMV, a member of the b-herpesvirus family, is a common human pathogen infecting 70–90% of the world’s population. It remains latent for lifetime in its host after primary infection and reactivates periodically. Cell-free virus can be detected in the breast milk of over 90% of lactating seropositive women and 30–40% of one-year-old children have seroconverted for HCMV [8]. Breast cancer is a leading cause of death among women worldwide. We aimed to examine whether HCMV is present in breast cancer and sentinel lymph node (SLN) metastases
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