Among the chemokines, the most interesting chemokine-receptor pair is the CXC chemokine receptor-4 (CXCR4) and its lone ligand, CXC chemokine ligand-12 (CXCL12). Muller demonstrated that CXCR4 is consistently expressed in human breast cancer cells, malignant breast tumor and metastasis tumors, while its ligand CXCL12 is preferentially expressed in the lungs, liver, bone

marrow, and lymph nodes [2]. Thus, it can be deduced that the CXCL12-CXCR4 axis may be associated with the metastasis of breast cancer cells to the lungs, liver, bone, and lymph nodes. Unlike PAK inhibitor CXCL12, however, CC chemokine ligand-21 (CCL21) – the ligand for CC chemokine receptor-7 (CCR7) – is highly expressed in the lymph nodes of breast cancer patients [5]. Thus, the CCR7-CCL21 axis can be said to assume an important role in lymph node metastasis

[6]. In this study, the expression of both CXCR4 and CCR7 is combined to evaluate their contribution in the lymph node metastasis of breast cancer. The importance of growth factors such as epidermal growth factor receptor (EGFR) and human epidermal buy JSH-23 growth factor receptor2 (HER-2/neu) has been established in the prognosis of breast cancer. Recently, several studies have revealed the crosstalk between CXCR4 and EGFR or HER-2/neu through transactivation by the CXCL12-CXCR4 axis. This study aims to verify the significance of CXCR4, CCR7 and their CXCL12 and CCL21 ligands, together with EGFR in the evaluation of metastasis

and the prognosis of breast cancer. Methods Patient selection and clinical data The study group was composed of 200 specimens selected from 284 cases (84 cases were excluded owing to the absence of follow-up status) of female primary invasive duct breast cancer cases diagnosed between January 1997 and December 2004 at the General Hospital Ureohydrolase of Tianjin Medical University. Patients’ records were retrieved and clinical data, histopathological record, and treatment information were all reviewed. All patients had not been subjected to chemotherapy and radiotherapy prior to surgical resection but had received chemotherapy following surgical operation. Follow-up information from all the patients were obtained by the authors themselves in August 2009 through visits or telephone interviews with either the patients or their relatives. Mean follow-up time was 88 months, ranging from 5 to 150 months. Formalin-fixed paraffin-embedded tumor materials and their lymph node tissues were acquired from the Department of Pathology of Tianjin Medical University’s General Hospital. Tumor diameter, pathologic stage, and nodal status were selected from the primary pathology reports. All slides were reviewed by two pathologists to define histological types and grades. Construction of TSA HDAC order tissue microarray Tissue microarray (TMA) blocks were constructed from formalin-fixed, paraffin-embedded breast cancer samples stored at the Department of Pathology of Tianjin General Hospital.