The Study Of The Relationship Between CXCR4,OPG In Tumor Growth And Spinal Metastasis Of Breast Cancer

Background:Spinal metastasis is that primary malignant neoplasms which is not derived from bone metastasize to the spine through the blood circulation, lymph circulation and other means. Incidence, disability and mortality of the spinal metastasis,which is serious harm to human health, is more than primary malignant spinal tumor. Spinal metastasis usually occurs in adults and the elderly,and its common disease sites were more common in thoracic and lumbar.As a common malignancy,breast cancer is a leading cause of morbidity and mortality,and a gradual increase in its in cadence has been recognized.Approximately 70% of breast cancer patients die from metastatic disease,even after complete resection of the primary tumor. Conditions that occurs with spinal metastases such as osteolysis of bone, collapse of vertebrae, instability of spine column and compression of spinal cord often lead to severe pain, neurofunctinal impairment even plegia, then result in decrease of life quallty and survival time.Surgical treatment takes an important position in therapy of spinal metastases, witch plays an irreplaceable role in removing of lesion, decompression of nerve, reconstruction of stability.Not only immunocytes but also tumor cells express chemokine receptors. Muller explained the relationship between chemokine receptors and breast cancer metastasis in 2001 and showed that the expression of chemokine receptors was significantly associated with tumor metastasis. CXC chemokine receptor 4 (CXCR4) is one of the most common chemokine receptors in tissues and plays important roles in malignant tumors growth, migration and metastasis.CXCR4 is expressed higher in tumors than in normal tissues, and organs representing the common sites of tumor metastasis are the most abundant sources of its ligand stromal cell derived factor-1(SDF-1).Signalling through CXCR4 mediates actin Polymerization and pseudopodia formation in cells, and induces chemotactic activity and migration to target organs. In addition, SDF-1/CXCR4 axis can promote tumor angiogenesis and growth. It plays an important role in the process of tumors infestation and metastasis.Osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor (OCIF), is a cytokine, which can inhibit the production of osteoclasts. At present, there are many reports about more expression in tumors such as gastric cancer, breast cancer, bronchogenic carcinoma, colon carcinoma, encephaloma, liver cancer than in innocuousness tissue. The expression of OPG can promote invasive growth of tumor.In our studies, we detect the expression of CXCR4,OPG so that to study the meaning of origining and developing in breast cancer.it can explain etiopathogenisis of breast cancer from multiple aspects and give new thinking for diagnosis and treatment of breast cancer.Methods:Collecting breast cancer specimens,lymphatic metastasis specimens,spinal metastasis specimens and innocuousness tissue specimens. Constructing one tissue arrayer, which contain 182 points. Immunohistochemistry was applied to detect the expression of CXCR4,OPG to observe the relationship among them. To further observe the relation between the expression of them and the associated clinicopathological features.Results:1,Constructing one tissue arrayer of 182 points, which contains 80 points of breast cancer,22points of innocuousness tissue,40 points of lymphatic metastasis,40 points of spinal metastasis.2,The positive expression of CXCR4,OPG protein colors cytomembrane and cytolymph with pale yellow, dark yellow or brown.The positive expression of CXCR4,OPG of breast cancer by IHC were 57.5%,65.5%, respectively. The expressions of CXCR4,OPG between breast cancer and non-tumor have a remarked difference (P<0.05).3,The positive expression of CXCR4,OPG of lymphatic metastasis by IHC were 65.0%, 60.0%, respectively. The expressions of CXCR4,OPG between breast cancer and lymphatic metastasis have no significance difference (P>0.05). The positive expression of CXCR4 of spinal metastasis by IHC were 85.0%. The expressions of CXCR4 between breast cancer and spinal metastasis have a remarked difference (P<0.05). The positive expression of OPG of spinal metastasis by IHC were 70.0%. The expressions of OPG between breast cancer and spinal metastasis have no significance difference (P>0.05).4,The expression of CXCR4, OPG had no relation with patient's age, ER, PR, pathological and TNM staging system in breast cancer (P>0.05). The expression of CXCR4, OPG had significance relation with lymph node metastasis in breast cancer (P<0.05).Conclusions:1,The level of CXCR4, OPG proteins in breast cancer tissue are more high than its in non-tumor tissue, and breast cancer occurrence and development are closely linked. 2,The level of CXCR4, OPG proteins are high expression in lymphatic metastasis and spinal metastasis, and had significance relation with metastasis in breast cancer.3,The level of CXCR4, OPG proteins of Breast cancer had significance relation with lymph node metastasis in breast cancer, that can be used as indicators of breast cancer predicting lymph node metastasis.