High Prevalence of Human Cytomegalovirus Proteins and Nucleic Acids in Primary Breast Cancer and Metastatic Sentinel Lymph Nodes

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.

Immunohistochemical detection of human cytomegalovirus, Epstein-Barr virus and human papillomavirus in invasive breast carcinoma in Egyptian women: A tissue microarray study

“…[5] However, we found that HCMV wasn't associated with tumor recurrence or patient death. The virus wasn't detected in non -tumor tissue or inflammatory cells in our study which is consistent with the results detected by Taher et al [31] In addition, others didn't find the virus in the fibroadenoma tissue. [19] EBV has been suggested to be associated with breast cancer indicated by detection of the virus in breast milk, presence of some EBV associated lymphomas in the breast and that breast cancer has epidemiological similarities to young adult Hodgkin's lymphoma.…”

“…Others found the virus proteins in 100% of cases and in the epithelial cells of metastasis in the sentinel lymph nodes suggesting its role in development of breast cancer and its metastasis. [31] It has been found that there is an association between HCMV and lower disease free and overall survival times. [5] However, we found that HCMV wasn't associated with tumor recurrence or patient death.…”

Expression of Oncogenic Alleles Induces Multiple Blocks to Human Cytomegalovirus Infection

“…HCMV has increasingly been implicated as an etiological agent in oncogenesis. HCMV genes have been found in a variety of human carcinomas but not in matched tissue controls (31)(32)(33)(34). HCMV nucleic acids and proteins have also been found to be associated with a high percentage of malignant gliomas and meduloblastomas (35)(36)(37)(38)(39).…”

Low Expression of Estrogen Receptor-α and Progesterone Receptor in Human Breast Cancer Tissues Is Associated With High-Grade Human Cytomegalovirus Protein Expression

“…Human cytomegalovirus (HCMV) has been detected in glioblastoma multiforme 14,15 , medulloblastoma 16 , neuroblastoma 17 , colon cancer 18,19 , and prostate cancer 20 , as well as in primary BC and sentinel lymph nodes and distant metastases from BC patients [21][22][23] . In general, increased viral activity is associated with worse prognosis.…”