| Backgroud and objectiveThyroid cancer is a common malignancy in head and neck. Its morbidity and mortality is the highest in head and neck malignancy. In recent years the incidence of thyroid cancer has a clear upward trend. The most common pathological type of thyroid cancer is papillary carcinoma. Papillary thyroid cancer is invasive growth and prone to lymph node metastasis in early stage. However, the main reason of patients with thyroid cancer treatment failure and death is recurrence and metastasis. Therefore, how to control thyroid cancer invasion and metastasis becomes a research hotspot.AnnexinⅡprotein is an important member of the calcium phospholipids binding protein family (Annexins). AnnexinⅡprotein plays an important role in a series of calcium-mediated cell activities such as biofilm accumulation, endocytosis and exocytosis, ion channel formation, cell proliferation and apoptosis, etc. There is overexpression of AnnexinⅡin breast cancer, colon cancer, lung cancer and other malignant tumors. AnnexinⅡprotein in the cell surface acts as the receptor of plasmin, plasminogen, t-PA, cathepsin B, S100A4, S100A10, etc and involves in the degradation process of basement membrane and extracellular matrix, and thereby promotes tumor's invasion and metastasis. Tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (uPA) are the main components of fibrinolytic system and they are belonging to the serine protease family. The main biological function of t-PA and uPA is activating plasminogen to plasmin. So t-PA and uPA play an important role in physiological processes such as physiological hemostasis, thrombosis degradation, tissue repair, etc. In addition, many tumor cells have also the expressions of t-PA and uPA. The plasmin activated by t-PA and uPA can cause the degradation of basement membrane and extracellular matrix protein and play an important role in the tumor's invasion and metastasis. The effect of t-PA in intravascular thrombolysis process is stronger than uPA, but the effect in tumor development is weaker than that of uPA. uPA protein influences the invasion and metastasis of tumor through a variety of mechanisms such as activating plasmin, promoting angiogenesis, initiating signal transduction.The research about combined detection of AnnexinⅡ, t-PA, uPA proteins expression in thyroid cancer and its relationship with tumor has not been reported. To explore the relationship between the three proteins and the development of thyroid cancer and to explore the relationship among the three proteins, the present study detects the expressions of AnnexinⅡ, t-PA, uPA proteins in normal thyroid tissue, nodular goiter, adenoma and papillary cancer tissues by immunohistochemistry, and explore the role of AnnexinⅡ, t-PA, uPA proteins in the development and lymph node metastasis of thyroid cancer from protein levels. Thus it can provide the basis for early diagnosis and the malignant degree assessment of thyroid cancer, and can provide an effective target for the gene therapy of thyroid cancer.Materials and methods1. Using the technology of immunohistochemistry (SP) to detect the expressions of AnnexinⅡ, t-PA, uPA proteins in the 35 cases of papillary thyroid cancer tissues,10 cases of thyroid adenoma tissues,16 cases of nodular goiter tissues and 7 cases of normal thyroid tissues.2. Statistical analysis:All the datas were analyzed by SPSS 13.0 statistical software package. The comparison of positive rates uses the Chi-square; the correlation of two variables is analyzed by the Spearman's correlation analysis. The level of significant difference isα=0.05.Results1. The positive expression rate of AnnexinⅡprotein was 14.29%(1/7) in normal thyroid tissues,31.25%(5/16) in nodular goiter tissues,30.00%(3/10) in thyroid adenoma tissues and 74.29%(26/35) in papillary thyroid cancer tissues. The positive expression rate of AnnexinⅡprotein in papillary thyroid cancer was significantly more than that in normal thyroid tissues, nodular goiter tissues and thyroid adenoma tissues, and the differences were statistically significant. The comparisons between every two groups of normal thyroid tissues, nodular goiter tissues and thyroid adenoma tissues were no statistically significant. The expression of AnnexinⅡprotein in cancer tissues associated with tumor size and lymph node metastasis, but no association with the patients' sex and age. The positive expression rate of AnnexinⅡprotein in the male group was 60.00%(3/5), and 76.67%(23/30) in the female group, the difference was no statistically significant. The positive expression rate of AnnexinⅡprotein in the group with patients' age≥45 years was 73.33%(11/15), and 75.00%(15/20) in the group with patients' age< 45 years, the difference was no statistically significant. The positive expression rate of AnnexinⅡprotein in the group with tumor diameter≥1.0cm was 86.96%(20/23), significantly increased than that in the group with tumor diameter< 1.0cm (50.00%,6/12), the difference was statistically significant. The positive expression rate of AnnexinⅡprotein in the group with lymph node metastasis was 94.44%(17/18), significantly increased than that in the group without lymph node metastasis (52.94%,9/17), the difference was statistically significant.2. The positive expression rate of t-PA protein was 28.57%(2/7) in normal thyroid tissues,43.75%(7/16) in nodular goiter tissues,60.00%(6/10) in thyroid adenoma tissues and 85.71%(30/35) in papillary thyroid cancer tissues. The positive expression rate of t-PA protein in papillary thyroid cancer was significantly more than that in normal thyroid tissues and nodular goiter tissues. But there was no statistically significant between papillary thyroid cancer and thyroid adenoma tissues. The comparisons between every two groups of normal thyroid tissues, nodular goiter tissues and thyroid adenoma tissues were no statistically significant. The expression of t-PA protein in cancer tissues has no association with patients'sex and age, tumor size and lymph node metastasis. The positive expression rate of t-PA protein in the male group was 80.00%(4/5), and 86.67%(26/30) in the female group, the difference was no statistically significant. The positive expression rate of t-PA protein in the group with patients' age≥45 years was 86.67%(13/15), and 85.00%(17/20) in the group with patients' age<45 years, the difference was no statistically significant. The positive expression rate of t-PA protein in the group with tumor diameter≥1.0cm was 86.96%(20/23), and 83.33%(10/12) in the group with tumor diameter<1.0cm, the difference was no statistically significant. The positive expression rate of t-PA protein in the group with lymph node metastasis was 88.89%(16/18), and 82.35%(14/17) in the group without lymph node metastasis, the difference was no statistically significant.3. The positive expression rate of uPA protein was 14.29%(1/7) in normal thyroid tissues,18.75%(3/16) in nodular goiter tissues,40.00%(4/10) in thyroid adenoma tissues and 88.57%(31/35) in papillary thyroid cancer tissues. The positive expression rate of uPA protein in papillary thyroid cancer was significantly more than that in normal thyroid tissues, nodular goiter tissues and thyroid adenoma tissues, and the differences were statistically significant. The comparisons between every two groups of normal thyroid tissues, nodular goiter tissues and thyroid adenoma tissues were no statistically significant. The expression of uPA protein in cancer tissues associated with lymph node metastasis, but no association with the patients' sex, age and tumor size. The positive expression rate of uPA protein in the male group was 80.00%(4/5), and 90.00%(27/30) in the female group, the difference was no statistically significant. The positive expression rate of uPA protein in the group with patients' age≥45 years was 86.67%(13/15), and 90.00%(18/20) in the group with patients' age< 45 years, the difference was no statistically significant. The positive expression rate of uPA protein in the group with tumor diameter≥1.0cm was 91.30% (21/23), and 83.33%(10/12) in the group with tumor diameter<1.0cm, the difference was no statistically significant. The positive expression rate of uPA protein in the group with lymph node metastasis was 100.00%(18/18), significantly increased than that in the group without lymph node metastasis (76.47%,13/17), the difference was statistically significant.4. There was a positive correlation between the expression of AnnexinⅡprotein and t-PA protein in papillary thyroid cancer tissues (r=0.507, P< 0.05).5. There was a positive correlation between the expression of AnnexinⅡprotein and uPA protein in papillary thyrdid cancer tissues (r=0.405, P< 0.05).6. There was a positive correlation between the expression of t-PA protein and uPA protein in papillary thyroid cancer tissues (r=0.367, P< 0.05).Conclusions1. The expressions of AnnexinⅡ, t-PA, uPA proteins in papillary thyroid cancer were higher than normal thyroid tissue and benign lesions. And all of these three proteins'expressions have gradually increased from normal tissues, benign lesions to malignant tumors. It suggests that AnnexinⅡ, t-PA, uPA proteins may be involved in the occurrence and development of papillary thyroid cancer.2. With the increase of the diameter of papillary thyroid cancer, the expression of AnnexinⅡprotein has gradually increased. It indicates that Annexinll protein may be involved in the growth of papillary thyroid cancer. With the emergence of lymph node metastasis, the expressions of AnnexinⅡprotein and uPA protein have gradually increased. It indicates that Annexinll, uPA protein play a facilitating role in the lymph node metastasis of papillary thyroid cancer.3. The correlations between every two proteins of AnnexinⅡ, t-PA, uPA protein expressions in papillary thyroid cancer were positive. It suggests that the expressions of these three proteins were consistent and played a synergistic effect in the occurrence and development of papillary thyroid cancer. |
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