IDO has been reported to induce immunotolerance and promote metastasis in solid malignancy, but the mechanisms involved were not fully understood. In this study, the expression of IDO in primary breast cancer was examined and the correlation between the expression levels of IDO and the densities of Foxp3+ Tregs in situ was studied. The IDO stably-expressing CHO cells(IDO/CHO) were generated to evaluate the induction of Foxp3+ Tregs after coculturing with CD3+ T cells in vitro. The IDO expression in cancer was higher than that in benign diseases both at RNA and protein levels. The IDO expression was significantly upregulated in tumors of more advanced stages and with more extensive lymph node metastasis, and displayed positive linear correlation with the density of Foxp3+ Tregs. We further demonstrated that CD4+CD25+CD127− Tregs could be amplified by coculturing CD3+ T cells with IDO/CHO cells in vitro which displayed increasing Foxp3 expression both at mRNA and protein levels. Our results implied that up-regulation of IDO in primary breast cancer may inhibit local immune surveillance and promote metastasis by favoring development and infiltration of Foxp3+ Tregs in the tumor microenvironment.

Abstract. Nine cases of infiltrating cribriform carcinoma (ICC) of the breast are reported and the clinicopathological features, particularly the imaging findings, are analyzed in the present study. Sonograms revealed that all masses exhibited a hypoechoic internal echo texture (9/9) and that a number of masses presented with an irregular shape (8/9), obscure boundary (5/9), partially microlobulated (5/9) or well-circumscribed (4/9) margins, and an inhomogeneous echo (8/9). Mammographic imaging revealed increased radiological density masses (6/8), and sand-like calcification was not observed in all patients. In two patients, the tumors were mammographically occult. Magnetic resonance imaging performed on one patient revealed a slightly high signal intensity on fat-saturated T1-and T2-weighted images. Following contrast enhancement, a homogeneous early enhancement was revealed with a quick ascent and quick descent time-density curve. Immunohistochemistry revealed that all ICCs expressed estrogen receptor and progesterone receptor, but that none were positive for human epidermal growth factor receptor 2. The Ki-67 labeling index was 3.75% (range, 2-5%) in the tumor tissue. Four patients were treated with mastectomy and the others with breast-conserving surgery. Six clinically node-negative patients underwent sentinel lymph node biopsy; three then received axillary lymph node dissection. Following surgery, three patients received adjuvant chemotherapy, radiotherapy and hormonal therapy, respectively. With a median follow-up time of 38 months (range, 4-70 months), one patient developed local recurrence following breast-conserving surgery; axillary lymph nodes and distant metastases were not observed. This study confirms that this type of carcinoma has unique biological characteristics and a favorable prognosis, but that it remains possible to experience local recurrence. IntroductionInfiltrating cribriform carcinoma (ICC) of the breast, which is characterized by a predominant cribriform growth pattern of its invasive component, is a distinct histological type of invasive carcinoma first described by Page et al in 1983 (1). The incidence of ICC is reported to range from 0.3 to 3.5% (1-4). The carcinoma has a low frequency of axillary nodal metastases and a favorable prognosis (2). Previous immunohistochemical studies (2,5-7)have revealed that the majority of patients with ICC exhibited estrogen receptor (ER) and progesterone receptor (PR) positive tumors, while human epidermal growth factor receptor 2 (HER2) amplification was rarely observed (5). For this reason, some people recommended that this favorable histotype with luminal tumor may be suitable for no therapy or endocrine therapy alone (8). However, no standard treatment guidelines exist for ICC and thus, treatment is mostly based on that for invasive ductal carcinoma (IDC). Clinically, the tumor usually presents as a mass, but is frequently asymptomatic. The tumor is not usually detected by mammography, but may be identified as a non-malignant mass on sonograp...

Breast cancer (BC) is a malignancy with high incidence among women in the world. This study aims to screen key genes and potential prognostic biomarkers for BC using bioinformatics analysis. Total 58 normal tissues and 203 cancer tissues were collected from three Gene Expression Omnibus (GEO) gene expression profiles, and then the differential expressed genes (DEGs) were identified. Subsequently, the Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway were analyzed to investigate the biological function of DEGs. Additionally, hub genes were screened by constructing a protein-protein interaction (PPI) network. Then, we explored the prognostic value and molecular mechanism of these hub genes using Kaplan-Meier (KM) curve and Gene Set Enrichment Analysis (GSEA). As a result, 42 upregulated and 82 down-regulated DEGs were screened out from GEO datasets. The DEGs were mainly related to cell cycles and cell proliferation by GO and KEGG pathway analysis. Furthermore, 12 hub genes (FN1,