| BackgroundLaryngeal squamous cell carcinoma (LSCC) is a malignant tumor derived from the laryngeal mucosa epithelium. It occurs with smoking, alcoholism, long-term inhalation of harmful substances and papilloma virus infection and other factors. It is a common malignancy otorhinolaryngology in the ENT field with nasopharyngeal and nasal sinus cancer. The incidence of LSCC accounts for approximately 1～5%of systemic cancer, and it is most common between the age of 45 and 75 years. At present,men are more frequently affected than women. The LSCC'incidence of people in the city was significantly higher than in rural areas. In recent years, the incidence has gradually increased especially in the young man. For patients of definitive LSCC, A good therapeutic efficacy can be get through laryngectomy. The overall 5 year survival rates are 80%after laryngectomy. For those Patients with cervical lymph node metastasis,the overall 5 year survival rates are 46.2%after laryngectomy,even though through radical neck disseetion and postoperation radiotherapy. Mortality rate increased significantly. Metastasis of tumor cells is a very complicated process. The chemokine and its receptor are closely related to the performance of malignant tumor cells,especically the CXCL12/CXCR4 interactions,which play an important role in a variety of tumor's growth, proliferation, invasion and metastasis. Chemokine regulate infiltration of leukocyte to the tumor, causing the immune response to kill the tumor cells and promoting of tumor-associated angiogenesis, to autocrine or paracrine manner in order to stimulate tumor cell proliferation, for tumor cells invasion through breaking the basement membrane,to promote cancer movement and distant metastasis. With high expression of tumor cell-specific chemokine receptors and high expression of their corresponding chemokine ligands in some organs,tumor cells transfer to these specific-organ through the binding specificity of chemokine and its receptor. In lots of tumors, CXCL12/CXCR4 were found involving in the tumor local invasion and organ-specific metastasis.ObjectiveBy observing the expression of chemokine CXCL12 and its receptor CXCR4 in laryngeal squamous cell carcinoma,to explore the CXCL12-CXCR4 biological axis and clinical pathological features of laryngeal squamous cell carcinoma, tumor size, invasion and metastasis of the relationship between behavior and prognosis,to provide a theoretical basis for the clinical treatment.Materials and Methods1. MaterialsSpecimens of squamous cell carcinoma were obtained from 77 outpatients in the department of Otorhinolaryngology from August 2008 to December 2009,in the First Affiliated Hospital of Zhengzhou University. It is confirmed to be squamous cell carcinoma after postoperative pathological examination. Selecting 18 cases from adjacent normal mucosa. The clinical and pathological information of all cases is complete,without radiotherapy, chemotherapy and any other treatment before operation.2,MethodsSP immunohistochemistry method was used to measure the expression of CXCL12, CXCR4 in human laryngeal carcinoma and adjacent normal tissue. We can get half quantitation ranking scores according to stain intensity. Percentage of positive cells≤10%:0 point.11%to 25%:1 point,26%to 50%:2 points,51%to 75%:3 points,≥76%as 4 points. Color intensity:no color:0 point, pale yellow,1 point; yellow,2 points; brown,3 points. Taking the product of these two scores as the total score:0 is divided into negative (-),1 to 4 were divided into weak positive (+),6 to 8 is divided into positive (++),9 to 12 are divided into strongly positive (+++).3,Statistical analysisSPSS 13.0 statistical package was used for data analysis and The data was analyzed by x2 test and Spearman rank correlation analysis. P<0.05 shows statistical significance.Results1,The expression of CXCR4 protein in carcinoma tissues and normal tissuesPositive expression rate of CXCR4 in 77 patients with laryngeal carcinoma was 63.64%(49/77). CXCR4 protein were located in the cytoplasm or/and cell membranes of laryngeal cancer cells, but not in the normal stromal cells. The positive expression rate of CXCR4 in laryngeal cancer cells was significant higher than that in normal controls (x2=12.991, P< 0.05). There was a significant difference in the positive rates of CXCR4 between the two groups (P<0.05). and the expression intensity between the two groups was statistically significant (x2=13.778,P 0.05). The expression of CXCR4 had significant relations with lymph node metastasis and T staging(P<0.05).2,The expression of CXCL12 protein in carcinoma tissues and normal tissuesPositive expression rate of CXCL12 in 77 patients with laryngeal carcinoma was 55.84%(43/77). CXCL12 protein expressed in the cytoplasm and nucleus of laryngeal squamous cell, but the mainly cytoplasm. Positive expression rate of CXCL12 in 10 normal patients was 44.44%(8/18). The positive expression rate of the two groups was not statistically significant (x2=0.763,P>0.05), and the intensity of positive expression between two groups was not statistically significant difference (x2=5.861,P>0.05). The expression of CXCL12 had significant relations with lymph node metastasis (P<0.05).3,The correlation analyse of expression of CXCR4, CXCL12 in LSCCPositive correlation was observed by Spearman rank correlation analysis between the expression of CXCR4, CXCL12 in Laryngeal squamous cell carcinoma.(r= 0.252, p<0.05).Conclusion1,The expression rate and intensity of positive expression of CXCR4 in laryngeal tissue aer significantly higher than the adjacent normal laryngeal tissue. It may be related to the growth and proliferation of laryngeal squamous cell carcinoma.2,The results show that CXCL12 protein is a evident in the expression of adjacent lymph nodes. The positive expression rate of CXCL12 between LSCC and the normal tissue is not statistically significant. Normal stromal cells can also secrete chemokines.3,There is a positive correlation between the expression of CXCL12 and CXCR4 in laryngeal carcinoma (P<0.05). Combination of CXCL12 and CXCR4 active the downstream signaling pathway, promotes cell survival and proliferation and tumor invasion and metastasis.
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