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

摘要

Micro-Abstract The mechanisms involved in initiation and progression of breast cancer (BC), the most common malignancy and second leading cause of cancer deaths in women, are largely unknown. Human cytomegalovirus (HCMV) has been detected in primary BC, sentinel lymph nodes, and brain metastases of BC patients. Here, we found HCMV DNA, RNA, and proteins in BC, and their prevalence was higher in advanced cancer. HCMV levels correlated inversely with estrogen ( P ?= .02) and progesterone ( P ?= .003) receptor expression. HER2 expression was also found to be decreased in HCMV-positive samples without reaching a level of statistical significance ( P ?= .09). Our findings showing that high-grade expression of HCMV immediate-early protein correlated negatively with hormone receptor expression, suggest a role for HCMV in the development of hormone receptor-negative BC in subgroups of patients, possibly by hampering hormone receptor expression and forcing BC cells into a more aggressive and hormone-independent phenotype. Abstract Background The underlying mechanisms for breast cancer (BC) are largely unknown. We investigated possible correlations between the expression levels of human cytomegalovirus (HCMV) proteins and established histopathological markers of BC, including expression of estrogen receptor (ER)-α, the progesterone receptor (PgR), and HER2. Materials and Methods We retrospectively examined paraffin-embedded biopsy specimens of BC (n?= 62), ductal carcinoma in situ (n?= 19), and adjacent normal breast tissue (n?= 42) for HCMV immediate-early protein (IE), HCMV late antigen, HCMV DNA and RNA, and investigated possible correlations between them and expression of ER-α, PgR, and HER2. Results HCMV DNA and RNA were detected in all examined infiltrating BCs. High-grade positivity for HCMV-IE was detected in 77% of infiltrating BCs, 39% of ductal carcinomas in situ, and 7% of tumor-free breast tissue samples. HCMV expression correlated inversely with ER-α ( P ?= .02) and PgR ( P ?= .003) expression. HER2 expression was also reduced in HCMV-positive samples without reaching a level of statistical significance ( P ?= .09). Conclusion The negative correlation between high-grade expression HCMV-IE and hormone receptor expression suggests a role for HCMV in hormone receptor-negative BC tumors, possibly by forcing BC cells into a more aggressive phenotype.