Inflammatory Breast Cancer: High Incidence of Detection of Mixed Human Cytomegalovirus Genotypes Associated with Disease Pathogenesis

Abstract

Inflammatory breast cancer (IBC) is a highly metastatic, aggressive, and fatal form of breast cancer. Patients presenting with IBC are characterized by a high number of axillary lymph node metastases. Recently, we found that IBC carcinoma tissues contain significantly higher levels of human cytomegalovirus (HCMV) DNA compared to other breast cancer tissues that may regulate cell signaling pathways. In fact, HCMV pathogenesis and clinical outcome can be statistically associated with multiple HCMV genotypes within IBC. Thus, in the present study, we established the incidence and types of HCMV genotypes present in carcinoma tissues of infected non-IBC versus IBC patients. We also assessed the correlation between detection of mixed genotypes of HCMV and disease progression. Genotyping of HCMV in carcinoma tissues revealed that glycoprotein B (gB)-1 and glycoprotein N (gN)-1 were the most prevalent HCMV genotypes in both non-IBC and IBC patients with no significant difference between patients groups. IBC carcinoma tissues, however, showed statistically significant higher incidence of detection of the gN-3b genotype compared to non-IBC patients. The incidence of detection of mixed genotypes of gB showed that gB-1 + gB-3 was statistically significantly higher in IBC than non-IBC patients. Similarly, the incidence of detection of mixed genotypes of gN showed that gN-1 + gN-3b and gN-3 + gN-4b/c were statistically significant higher in the carcinoma tissues of IBC than non-IBC. Mixed presence of different HCMV genotypes was found to be significantly correlated with the number of metastatic lymph nodes in non-IBC but not in IBC patients. In IBC, detection of mixed HCMV different genotypes significantly correlates with lymphovascular invasion and formation of dermal lymphatic emboli, which was not found in non-IBC patients.

Distribution of cytomegalovirus genotypes among ulcerative colitis patients in Okinawa, Japan

“… 34 The gN3b genotype was reported as the most prevalent genotype in a study of patients with inflammatory breast cancer. 35 However, gN3 was not found to be frequently associated with other populations of immunocompromised patients. By contrast, gN1 has been frequently observed among solid organ transplant patients and acquired immunodeficiency syndrome patients.…”

Human cytomegalovirus interleukin-10 enhances matrigel invasion of MDA-MB-231 breast cancer cells

“…They reported detection of more HCMV DNA in IBC tissues compared to IDC, and higher HCMV IgG titers in IBC patients compared to IDC patients [ 72 ]. In a follow-up study, they assessed viral genotypes and found a correlation between mixed phenotypes and disease progression, notably lymphovascular invasion and formation of lymphatic emboli in IBC patients, but not in women with other forms of breast cancer [ 73 ]. The findings suggest that HCMV may be more closely associated with specific subtypes of breast cancer.…”

Cytomegalovirus IgG and IgM antibodies among Sudanese patients with acute myeloid leukemia: relation to hematological prognostic markers

“…[8] and in carcinoma tissue of malignant glioma [9] and prostate cancer [10]. CMV is reported to have an oncogenic potential role in breast cancer [11] and to have possible causal relationship with mucoepidermoid carcinoma [12] .…”