Protein and DNA evidences of HCMV infection in primary breast cancer tissues and metastatic sentinel lymph nodes

Article type: Research Article

Authors: Cui, Jian^a | Wang, Qian^b | Wang, Hai-Bo^{a; *} | Wang, Bin^b | Li, Ling^b

Affiliations: [a] Breast Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266071, China | [b] Department of Microbiology, Qingdao University Medical College, Qingdao, Shandong 266071, China

Correspondence: [*] Corresponding author: Hai-Bo Wang, Breast Center, The Affiliated Hospital of Qingdao University, No. 59 of Haier Road, Laoshan District, Qingdao, Shandong 266071, China. Tel.: +86 186 6180 5216; Fax: +86 8291 3555; E-mail: [email protected].

Abstract: BACKGROUND AND OBJECTIVE: Breast cancer is the leading cause of death in women worldwide. There are evidences that human cytomegalovirus (HCMV) infection is associated with several malignant tumors. This study aims to investigate the infection of human cytomegalovirus (HCMV) in a large sample of breast cancer patients, and conduct a correlation analysis of clinical and pathological factors, to provide evidence for whether HCMV infection is associated with breast cancer development, progression and metastasis. MATERIALS AND METHODS:A total of 438 tissue samples (including breast cancer tissue, paracancerous tissue and sentinel lymph node [SLN] tissue) obtained from 146 patients who were diagnosed with breast cancer and intraoperatively underwent unilateral axillary SLN biopsy at the Affiliated Hospital of Qingdao University from June 2013 to June 2014 were included into this study. These tissue samples were divided into two groups: SLN positive group and SLN negative group. The clinical information is collated and numbered. Normal breast tissues of 40 patients with cyclomastopathy were taken as controls. The expressions of HCMV immediate-early (IE) and late antigen (LA) proteins of breast cancer tissues, paracancerous tissues, SLN tissues and normal breast tissues were analyzed by immunohistochemistry, and HCMV infection of the samples was graded according to the percentage of the positive cells, and HCMV IE2 mRNA expression was detected by reverse transcription polymerase chain reaction. The clinical data were collated and statistically analyzed. RESULTS: HCMV IE and LA proteins were highly expressed in all breast cancer tissue samples. IE proteins were detected in 47.9% (70/146) of paracancerous tissue samples, and LA proteins were detected in 53.4% (78/146) of paracancerous tissue samples. IE and LA proteins were expressed in 92.6% of metastatic SLN samples (62/68) and in most of the tumor cells. Inflammatory cells in 60% (42/70) of non-metastatic samples were positive for HCMV. HCMV DNA was present in 100% of breast cancer tissue samples, 50% of paracancerous tissue samples, and 91% of metastatic SLN samples; but this was not present in HCMV negative and non-metastatic SLN samples. Differences in HCMV infection, and estrogen receptor-α, progesterone receptor, Elston classification, Ki67 percentage, Her-2 and Luminal type and other clinical indicators were not statistically significant. CONCLUSION:HCMV infection is common in breast cancer tissues, paracancerous tissues and SLN tissues. The severity of HCMV infection varied markedly with tissue type. HCMV infection might be associated with metastasis and invasion of breast cancer. The expression of HCMV IE2 was associated to breast cancer and lymph node metastasis. The expression level of estrogen receptor-α was related to HCMV infection.

Keywords: Primary breast cancer, HCMV, para cancer tissues, sentinel lymph nodes, immunohistochemistry

DOI: 10.3233/CBM-170409

Journal: Cancer Biomarkers, vol. 21, no. 4, pp. 769-780, 2018