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

• Published in: Clinical breast cancer Vol. 17; no. 7; pp. 526 - 535.e1
• Main Authors: Rahbar, Afsar, Touma, Joel, Costa, Helena, Davoudi, Belghis, Bukholm, Ida Rashid, Sauer, Torill, Vetvik, Katja, Geisler, Jürgen, Naucler, Cecilia Söderberg
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2017
• Subjects: Antigens, Viral - metabolism; Biomarkers, Tumor - metabolism; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Carcinoma, Ductal, Breast - metabolism; Carcinoma, Ductal, Breast - pathology; Carcinoma, Intraductal, Noninfiltrating - metabolism; Carcinoma, Intraductal, Noninfiltrating - pathology; Carcinoma, Lobular - metabolism; Carcinoma, Lobular - pathology; Estrogen receptor; Estrogen Receptor alpha - metabolism; Female; Follow-Up Studies; Hematology, Oncology and Palliative Medicine; Human cytomegalovirus; Human epidermal growth factor receptor 2; Humans; Immediate-Early Proteins - metabolism; Medicin och hälsovetenskap; Middle Aged; Neoplasm Grading; Obstetrics and Gynecology; Progesterone receptor; Receptors, Progesterone - metabolism; Retrospective Studies; breast cancer; human epidermal growth factor receptor 2; human cytomegalovirus; estrogen receptor-α; progesterone receptor; Estrogen receptor; Breast cancer; Progesterone receptor; Human epidermal growth factor receptor 2; Human cytomegalovirus
• ISSN: 1526-8209; 1938-0666; 1938-0666
• DOI: 10.1016/j.clbc.2017.04.013

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-α (ER- α), the progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2). Material 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 = 0.02 ) and PgR ( p = 0.003 ) expression. HER2 expression was also reduced in HCMV-positive samples without reaching a level of statistical significance ( P = 0.09 ). 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.