High prevalence of human cytomegalovirus proteins and nucleic acids in primary breast cancer and metastatic sentinel lymph nodes

PLoS One. 2013;8(2):e56795. doi: 10.1371/journal.pone.0056795. Epub 2013 Feb 22.

Abstract

Background: Breast 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 methods: Formalin-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.

Results: HCMV 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.

Conclusions: The 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / virology*
  • Cytomegalovirus / genetics*
  • Cytomegalovirus / metabolism*
  • Cytomegalovirus / pathogenicity
  • Female
  • Humans
  • Immunohistochemistry
  • In Vitro Techniques
  • Lymph Nodes / metabolism*
  • Lymph Nodes / virology*
  • Middle Aged
  • Real-Time Polymerase Chain Reaction
  • Sentinel Lymph Node Biopsy
  • Viral Proteins / genetics*
  • Viral Proteins / metabolism*

Substances

  • Viral Proteins

Grant support

This work was supported by RATOS, the Ragnar Söderbergś Research Foundation, the Swedish Research Council, the Swedish Children Cancer Research Foundation, the Swedish Cancer Foundation, Swedish Society for Medical Research (SLS), Percy Falks foundation, The Royal Swedish Academy of Sciences (KVA), Goljes Memory Foundation, Magnus Bergvalls Foundation, Tore Nilsons Foundation, and CT was supported by a scholarship from Kurdistan Regional Government/Iraq. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.