br The human CD molecule
The human CD155 molecule was first discovered by Mendelsohn et al. in 1989 . Since its structure is similar to that of Nectins, it is also known as Necl-5, and it participates in intercellular adhesion. It can mediate poliovirus invasion into the human body and cause polio;
therefore, it is also called the poliovirus receptor. CD155 is a Type 1 transmembrane glycoprotein with a molecular weight of approximately 70 Kda, and it belongs to the immunoglobulin superfamily [6,7]. Some in vitro experiments revealed that the CD155 molecule induced NK cell activation and killed tumor Pertussis Toxin by binding to the CD226 and CD96 molecules. Many studies have shown that CD155 is overexpressed in a variety of malignant tumors, such as colorectal carcinoma, gastric cancer, lung adenocarcinoma, ovarian cancer, melanoma, and neuro-blastoma [7–11]. However, the expression of CD155 has rarely been reported in BC.
Ki67 has been considered as an important biomarker of proliferation since 1980s. In recent years, together with ER, PR and HER-2, it has become an important part of routine biomarkers for BC [12,13]. The tumour–node–metastasis (TNM) staging system was first published by the American Joint Commission of Cancer (AJCC) in 1959 . The purpose of the BC TNM staging system is to predict prognosis and guide patients whether to receive adjuvant chemotherapy, endocrine therapy or anti- HER-2 therapy. Lymph node metastasis in breast cancer
1 These authors contributed equally to this work.
Characteristics n CD155+ Pearson x2 P-value
suggests a poor prognosis. CD163 has been proved to be a phenotypic marker mainly expressed on M2 macrophages and involved in anti-in-flammatory functions [15,16]. CD8 is expressed in a subgroup of NK cells , and CD8 + T cells are an important part of the cellular im-mune system and essential in cell-mediated anti-tumor immune re-sponses . CD68 was initially identified as a KP1 monoclonal anti-body that recognizes epitopes in a variety of different tissue macrophages, including germinal center, granulocyte precursors, splenic and laminapropria macrophages, and Kupffer cells . CD163/CD8/CD68 are three common tumor-infiltrating lymphocytes (TILs) closely related to tumor immunity. In our study, IHC and tissue microarray (TMA) technology were used to detect the expression of CD155 and the above clinical parameters in BC.
2. Materials and methods
2.1. Patients and specimens
In this study, data of 216 postoperative patients with BC were col-lected from January 2016 to December 2018 at Nanjing First Hospital, Nanjing Medical University, China. The following eligibility criteria were included in our study: (1) the histopathological classification and grading of BC met WHO criteria; (2) R0 resection of tumor lesions; (3) no preoperative anti-cancer treatment such as chemotherapy and
radiotherapy; (4) complete postoperative follow-up data; (5) no other primary or familial malignancies. All patients underwent TNM staging according to the 7th edition of AJCC system. OS was defined as death from any cause from the time of surgery. The study was approved by the Ethical Committee of Nanjing Medical University, and written in-formed consent was obtained for each patient prior to surgery. Patient age ranged from 30 to 80 years; 119 patients aged less than
60 years and 97 patients aged more than 60 years. In terms of history of menstruation, 91 patients were not yet menopausal and 125 patients were postmenopausal. In terms of histological classification, 26 cases were of ductal carcinoma, 173 cases were of lobular carcinoma, and 17 cases were of other types of cancer. In terms of ER status, 99 cases were ER positive and 117 cases were ER negative. In terms of PR status, 97 cases were PR positive and 119 cases were PR negative. In terms of HER-2 gene status, 96 cases were HER-2 positive and 120 cases were HER-2 negative. In terms of Ki-67 score, 130 cases had a Ki-67 score of more than 14% and 86 cases had a Ki-67 score of not more than 14%. In terms of primary tumor size, 104 cases were classified as T1, 97 cases as T2, 9 cases as T3, and 6 cases as T4. In terms of lymph node metastasis, 121 cases were classified as N0, 82 cases as N1, and 13 cases as N2 and N3. In terms of TNM staging, 89 cases were classified as stage I, 77 cases as stage II, and 50 cases as stage III. r> 2.2. TMA construction and IHC
TMAs were produced by using the Tissue Microarrayer System Quick-Ray (Unitma, Co., Ltd., Seoul, Korea) at the Department of Clinical Pathology, Nanjing First Hospital, Jiangsu, China. Core tumor tissues (diameter 2 mm), obtained from 216 postoperative patients with BC, were converted into formalin-fixed paraffin-embedded blocks and arrayed into new recipient paraffin blocks. Then these blocks were sliced, deparaffinized, and rehydrated through gradient alcohol. Endogenous peroxidase activity was inhibited by incubation with 3%