| Background and ObjectiveThyroid carcinoma is the most common endocrine malignancy, which represents 1% of all malignant diseases and 91.5% of all endocrine malignancies. Recent statistic shows that thyroid carcinoma's incidence is on the rise. According to the type of tumor pathology, thyroid carcinoma can be divided into papillary carcinoma, follicular carcinoma, undifferentiated carcinoma, medullary carcinoma. Papillary thyroid carcinoma is the most common type. This type has the tendency to encroach on local lymph node, some case may metastasis to distant place follow the blood. So it is necessary to explore the rule of invasion and metastasis of papillary thyroid carcinoma by take full advantage of modern immunology and molecular biology techniques. And it provides a reliable basis for clinical diagnosis and treatment. Cathepsin B (CB) is a proteolytic enzyme. It can hydrolyze vegetable protein (soy, corn, cottonseed protein, etc.) and animal protein (hemoglobin, serum protein, vitellin, gelatin, etc.). In vitro, cathepsin B can hydrolyze extracellular matrix such as fibronectin, I type collagen, IV collagen and laminin proteins,but also is able to activate urokinase-type plasminogen activator,matrix metalloproteinases. Tumor cells invade and metastasis by hydrolyzing extracellular matrix, so cathepsin B plays an important role in invasion and metastasis of tumor. CXC chemokine receptor 4 (CXCR4) belongs to G protein-coupled receptor superfamily. Stromal cell-derived factor 1 (SDF-1) is CXCR4's ligand. In recent years, many studies point out that CXCR4 / SDF-1 biological axis plays an important role in dissemination and organ-specific transfer of a variety of tumor. So some people offer a model of theory that tumor cells make specific organ metastasis come ture depending on chemokine. Tumor cells have a high expression of tumor-specific chemokine receptor. Some organs have a high expression of corresponding chemokine ligand. Tumor cells finally reach specific organ through binding between chemokine receptor and chemokine.The expression of cathepsin B in the papillary thyroid carcinoma, the relation between cathepsin B and invasion and metastasis of the papillary thyroid carcinoma and the relation between cathepsin B and CXCR4 in the invasion and metastasis of the papillary thyroid carcinoma has not been reported at home and abroad. In this study, the aim is to investigate the expression and correlation of cathepsin B and CXCR4 in the papillary thyroid carcinoma and discuss their role in the invasion and metastasis of the papillary thyroid carcinoma by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical SP method.Material and Method1. 40 cases of papillary thyroid carcinoma (PTC) and 10 cases of normal thyroid tissue had been collected from January 2005 to December 2007 at thyroid surgery of the first affiliated hospital of Zhengzhou University. All cases is diagnosed by experienced pathological doctor. All cases have not any treatment before operation. one part of specimens are put in liquid nitrogen to preserve for the extraction of RNA, another art of specimens are for immunohistochemistry.2. The expression of cathepsin B and CXCR4 in the papillary thyroid carcinoma are detected by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical SP method.3. SPSS10.0 statistical software is used for statistical analysis. Using the four data table x~2 test is for comparison of the rate of two samples. Using correlation analysis of spearman rank is for correlation analysis of two variables level. A P value of less than 0.05 is considered to be statistically significant. Results1. Positive staining for cathepsin B protein is mainly observed in the cytoplasm and is brown granules. Its positive rate in the papillary thyroid carcinoma is 65%(26/40).The expression of cathepsin B protein is not detected in normal thyroid tissue. The positive rate of cathepsin B protein has a significant difference between papillary thyroid carcinoma and normal thyroid tissue(P<0.05). The positive rate of cathepsin B mRNA in normal thyroid tissue is 0 and 82.5%(33/40) in the papillary thyroid carcinoma. The positive rate of cathepsin B mRNA has a significant difference between papillary thyroid carcinoma and normal thyroid tissue(P<0.05). Cathepsin B protein and mRNA in papillary thyroid carcinoma is not correlated with sex, age and tumor diameter(P>0.05).There is significant difference between the expression of cathepsin B protein and mRNA and the depth of invasion, lymph node metastasis(P<0.05).2. Positive staining for CXCR4 mRNA protein is mainly observed in the cytoplasm and is brown granules. Its positive rate in the papillary thyroid carcinoma is 60% (24/40) .The expression of CXCR4 protein is not detected in normal thyroid tissue. The positive rate of CXCR4 protein has a significant difference between papillary thyroid carcinoma and normal thyroid tissue(P<0.05). The positive rate of CXCR4 mRNA in normal thyroid tissue is 0 and 80% (32/40) in the papillary thyroid carcinoma. The positive rate of CXCR4 mRNA has a significant difference between papillary thyroid carcinoma and normal thyroid tissue(P<0.05). CXCR4 protein and mRNA in papillary thyroid carcinoma is not correlated with sex, age and tumor diameter(P>0.05).There is significant difference between the expression of CXCR4 protein and mRNA and the depth of invasion, lymph node metastasis(P<0.05).3. In 40 cases of papillary thyroid carcinoma, the expression of cathepsin B protein is positive correlated with that of CXCR4 (P<0.05).4. Using correlation analysis of spearman rank ,There is positive correlation between cathepsin B,CXCR4 mRNA and protein. In the same group , the expression rate of cathepsin B, CXCR4 mRNA is higher than the expression rate of cathepsin B, CXCR4 protein, and with the expression of cathepsin B, CXCR4 mRNA increasing, the expression of cathepsin B, CXCR4 protein also increases.Conclusions1. The expression of cathepsin B mRNA and protein is negative in normal thyroid. There is a high expression of cathepsin B mRNA and protein in the papillary thyroid carcinoma. The expression of cathepsin B mRNA and protein is significantly related to depth of invasion and lymph node metastasis of the papillary thyroid carcinoma. This hints cathepsin B is related to invasion and metastasis of the papillary thyroid carcinoma.2. The expression of CXCR4 mRNA and protein is negative in normal thyroid. There is a high expression of CXCR4 mRNA and protein in the papillary thyroid carcinoma. The expression of CXCR4 mRNA and protein is significantly related to depth of invasion and lymph node metastasis of the papillary thyroid carcinoma. This hints CXCR4 is related to invasion and metastasis of the papillary thyroid carcinoma.3. The positive correlation between the expression of cathepsin B protein and the expression of CXCR4 protein suggests that cathepsin B and CXCR4 protein may have a synergistic effect in invasion and metastasis of the papillary thyroid carcinoma.4. This study suggests that there is positive correlation between cathepsin B,CXCR4 mRNA and protein. In the same group , the expression rate of cathepsin B, CXCR4 mRNA is higher than the expression rate of cathepsin B, CXCR4 protein, and with the expression rate of CB, CXCR4 mRNA increasing, and the expression rate of CB, CXCR4 protein also increases. |
PDF Full Text Request