Expressions And Significances Of CD147,MMP-2 And AnnexinⅡ In The Tissue Of Papillary Thyroid Carcinoma

Background and objectiveThyroid carcinoma is one of common malignant tumors in head and neck and the most common malignant tumor in endocrine system. Its morbidity and mortality rank first in the head and neck malignancy. In recent years many data indicate that the incidence of thyroid carcinoma showed an upward trend year after year around the world. Thyroid carcinoma has the characteristics of highly invasion and transfer. And recurrence and metastasis are the main reasons for treatment failure and increased mortality of patients with thyroid carcinoma. Therefore, the things that control the development, invasion and metastasis of thyroid carcinoma become research hotspots in the field.The occurrence, development, invasion and metastasis of thyroid carcinoma are complex processes of multi-stage, multi-step and multiple factors. And a variety of genes and their protein products involved in these processes. CD147, the extracellular matrix metalloproteinase inducer, highly glycosylated, the molecular weight of 50-60KD, and widely expressed in various tissues of human, is a single transmembrane glycoprotein belonging to immunoglobulin superfamily. In recent years a large number of studies have shown that there is abnormally high expression of CD147 in a variety of tumor cells. And CD147 can promote invasion and metastasis of tumor cells mainly through inducing secretion of matrix metalloproteinases (MMPs). MMPs family is a highly conserved family of endogenous proteolytic enzymes and is a major regulator of extracellular matrix material, which can degrade almost all components of the extracellular matrix. MMP-2 is one of the main members of the family and plays an important role in the process of tumor's invasion and metastasis, because it mainly acts on the basement membrane collagen typeⅣand promotes tumor cells break through the basement membrane barrier. AnnexinⅡis one of the members of calcium-mediated phospholipids binding protein family and participates in a series of calcium ion-dependent membrane biological functions. There is highly expression of AnnexinⅡin many tumors. AnnexinⅡpromotes extracellular matrix degradation though interaction with tissue plasminogen activator (t-PA), plasminogen, plasmin, cell adhesion factor C, the former cathepsin B, S100A4, etc, thus speeding up the infiltration of tumor cells to surrounding tissue and lymph node metastasis and distant metastasis.The researches about combined detection of CD147, MMP-2, AnnexinⅡexpressions in thyroid carcinoma and their relationship with the occurrence and development of thyroid carcinoma have not been reported. To further explore the relationship between these three indicators and the occurrence, development and metastasis of thyroid carcinoma, to find early diagnosis indicators, evaluation factors of malignant degree, new therapeutic targets of thyroid carcinoma, the present study detects the expressions of CD147, MMP-2, AnnexinⅡproteins by immunohistochemistry and CD147mRNA by in situ hybridization in 50 cases of papillary thyroid carcinoma and 50 cases of non-cancerous tissues, and explore the relationship among CD147, MMP-2, AnnexinⅡand the possible mechanism. The aim is to clarify the relationship between expressions of CD147, MMP-2, AnnexinⅡand the occurrence, development and metastasis of thyroid carcinoma, and to provide experimental and theoretical basis for the diagnosis, assessment and treatment of papillary thyroid carcinoma. Methods1. Detected the expressions of CD 147, MMP-2, AnnexinⅡproteins in 50 cases of papillary thyroid carcinoma tissues,14 cases of thyroid adenoma tissues,26 cases of nodular goiter tissues and 10 cases of normal thyroid tissues by the technology of immunohistochemistry (SP).2. Detected the expression of CD147mRNA in 50 cases of papillary thyroid carcinoma tissues,14 cases of thyroid adenoma tissues,26 cases of nodular goiter tissues and 10 cases of normal thyroid tissues by in situ hybridization.3. Statistical analysis:All the dates were analyzed by SPSS17.0 statistical software package. The Chi-square was used for the comparison of positive rates; the Spearman's correlation analysis was used for analyzing the correlation of two variables. The level of significant difference is a=0.05.Results1. The positive rates of CD147 protein in papillary thyroid carcinoma, thyroid adenoma, nodular goiter and normal thyroid tissues were 76.00%(38/50),35.71% (5/14),34.62%(9/26) and 30.00%(3/10) respectively. The positive rates of CD147 protein in thyroid adenoma, nodular goiter and normal thyroid tissues were significantly lower than that in papillary thyroid carcinoma tissues, and the differences were statistically significant (P<0.05); The comparisons between any two groups of thyroid adenoma, nodular goiter and normal thyroid tissues were no statistically significant (P>0.05). The expression of CD 147 protein in papillary thyroid carcinoma tissues had no association with patients'sex and age. The positive rate of CD147 protein was 83.33%(5/6) in the male group,75.00%(33/44) in the female group, and the difference was no statistically significant (P>0.05); The positive rate of CD147 protein was 76.92%(20/26) in the group with age<45 years, 75.00%(18/24) in the group with age≥45 years, and the difference was no statistically significant (P>0.05). The expression of CD 147 protein gradually increased with the increase of the diameter of papillary thyroid carcinoma, and a positive correlation was showed between these two factors. The positive rate of CD147 protein was 55.00%(11/20) in the group with tumor diameter<1.0cm, 90.00%(27/30) in the group with tumor diameter≥1.0cm, and the difference was statistically significant (P<0.05). There was a positive correlation between the expression of CD147 protein in papillary thyroid carcinoma and lymph node metastasis. The positive rate of CD147 protein was 90.48%(19/21) in the group with lymph node metastasis,65.52%(19/29) in the group without lymph node metastasis, and the difference was statistically significant (P<0.05).2. The positive rates of MMP-2 protein in papillary thyroid carcinoma, thyroid adenoma, nodular goiter and normal thyroid tissues were 78.00%(39/50),42.86% (6/14),38.46%(10/26) and 30.00%(3/10) respectively. The positive rates of MMP-2 protein in thyroid adenoma, nodular goiter and normal thyroid tissues were significantly lower than that in papillary thyroid carcinoma tissues, and the differences were statistically significant (P<0.05); The comparisons between any two groups of thyroid adenoma, nodular goiter and normal thyroid tissues were no statistically significant (P>0.05). The expression of MMP-2 protein in papillary thyroid carcinoma tissues had no association with patients' sex and age. The positive rate of MMP-2 protein was 66.67%(4/6) in the male group,79.55%(35/44) in the female group, and the difference was no statistically significant (P>0.05); The positive rate of MMP-2 protein was 80.77%(21/26) in the group with age<45 years, 75.00%(18/24) in the group with age≥45 years, and the difference was no statistically significant (P>0.05). The expression of MMP-2 protein gradually increased with the increase of the diameter of papillary thyroid carcinoma, and a positive correlation was showed between these two factors. The positive rate of MMP-2 protein was 55.00%(11/20) in the group with tumor diameter<1.0cm, 93.33%(28/30) in the group with tumor diameter≥1.0cm, and the difference was statistically significant (P<0.05). There was a positive correlation between the expression of MMP-2 protein in papillary thyroid carcinoma and lymph node metastasis. The positive rate of MMP-2 protein was95.24%(20/21) in the group with lymph node metastasis,65.52%(19/29) in the group without lymph node metastasis, and the difference was statistically significant (P<0.05). 3. The positive rates of AnnexinⅡprotein in papillary thyroid carcinoma, thyroid adenoma, nodular goiter and normal thyroid tissues were 74.00%(37/50),35.71% (5/14),30.77%(8/26) and 10.00%(1/10) respectively. The positive rates of AnnexinⅡprotein in thyroid adenoma, nodular goiter and normal thyroid tissues were significantly lower than that in papillary thyroid carcinoma tissues, and the differences were statistically significant (P<0.05); The comparisons between any two groups of thyroid adenoma, nodular goiter and normal thyroid tissues were no statistically significant (P>0.05). The expression of AnnexinⅡprotein in papillary thyroid carcinoma tissues had no association with patients'sex and age. The positive rate of AnnexinⅡprotein was 66.67%(4/6) in the male group,75.00%(33/44) in the female group, and the difference was no statistically significant (P>0.05); The positive rate of AnnexinⅡprotein was 73.08%(19/26) in the group with age<45 years,75.00%(18/24) in the group with age≥45 years, and the difference was no statistically significant (P>0.05). The positive rate of AnnexinⅡprotein was 60.00%(12/20) in the group with tumor diameter<1.0cm,83.33%(25/30) in the group with tumor diameter≥1.0cm. With the increase of the diameter of papillary thyroid carcinoma, the expression of AnnexinⅡprotein gradually increased too but the difference between these two groups was no statistically significant (P>0.05). There was a positive correlation between the expression of AnnexinⅡprotein in papillary thyroid carcinoma and lymph node metastasis. The positive rate of AnnexinⅡprotein was 90.48%(19/21) in the group with lymph node metastasis,62.07% (18/29) in the group without lymph node metastasis, and the difference was statistically significant(P<0.05).4. The positive rates of CD147mRNA in papillary thyroid carcinoma, thyroid adenoma, nodular goiter and normal thyroid tissues were 74.00%(37/50),28.57% (4/14),26.92%(7/26) and 20.00%(2/10) respectively. The positive rates of CD147mRNA in thyroid adenoma, nodular goiter and normal thyroid tissues were significantly lower than that in papillary thyroid carcinoma tissues, and the differences were statistically significant (P<0.05); The comparisons between any two groups of thyroid adenoma, nodular goiter and normal thyroid tissues were no statistically significant (P>0.05). The expression of CD147mRNA in papillary thyroid carcinoma tissues had no association with patients'sex and age. The positive rate of CD147mRNA was 66.67% (4/6) in the male group,75.00% (33/44) in the female group, and the difference was no statistically significant (P>0.05); The positive rate of CD147mRNA was 76.92% (20/26) in the group with age<45 years, 70.83% (17/24) in the group with age≥45 years, and the difference was no statistically significant (P>0.05). The expression of CD147mRNA gradually increased with the increase of the diameter of papillary thyroid carcinoma, and a positive correlation was showed between these two factors. The positive rate of CD147mRNA was 45.00%(9/20) in the group with tumor diameter<1.0cm,93.33% (28/30) in the group with tumor diameter≥1.0cm, and the difference was statistically significant (P<0.05). There was a positive correlation between the expression of CD147mRNA in papillary thyroid carcinoma and lymph node metastasis. The positive rate of CD147mRNA was 90.48%(19/21) in the group with lymph node metastasis,62.07%(18/29) in the group without lymph node metastasis, and the difference was statistically significant (P<0.05).5. The co-expression positive rate of CD147, MMP-2, AnnexinⅡproteins in papillary thyroid carcinoma was 62.00%(31/50). The co-expression of these three proteins in papillary thyroid carcinoma had no association with patients'sex and age, but positively correlated with the tumor size and lymph node metastasis. The co-expression positive rate of CD147, MMP-2, AnnexinⅡproteins was 66.67%(4/6) in the male group,61.36%(27/44) in the female group, and the difference was no statistically significant (P>0.05); the co-expression positive rate of CD 147, MMP-2, Annexinll proteins was 62.50%(15/24) in the group with age≥45 years,61.54% (16/26) in the group with age<45 years, and the difference was no statistically significant (P>0.05). The co-expression positive rate of CD 147, MMP-2, AnnexinⅡproteins was 80.00%(24/30) in the group with tumor diameter≥1.0cm,35.00%(7/20) in the group with tumor diameter<1.0cm, and the difference was statistically significant (P<0.05). The co-expression positive rate of CD 147, MMP-2, AnnexinⅡproteins was 85.71% (18/21) in the group with lymph node metastasis,44.83% (13/29) in the group without lymph node metastasis, and the difference was statistically significant (P<0.05). 6. In papillary thyroid carcinoma tissues, there was a positive correlation between the expression of CD147 protein and MMP-2 protein (r=0.380, P<0.05); there was a positive correlation between the expression of CD 147 protein and AnnexinⅡprotein (r=0.521, P<0.05); there was a positive correlation between the expression of MMP-2 protein and AnnexinⅡprotein (r=0.676, P<0.05); there was a positive correlation between the expression of CD147 protein and CD147mRNA (r=0.735,P <0.05).Conclusions1. The positive expression rates of CD 147, MMP-2, AnnexinⅡproteins and CD 147 mRNA in normal thyroid, nodular goiter, thyroid adenoma, papillary thyroid carcinoma tissues showed gradually increasing trend. And the expressions in papillary thyroid carcinoma tissues were significantly higher than that in non-cancerous tissues. It suggests that CD147, MMP-2, AnnexinⅡproteins may be involved in the occurrence of thyroid carcinoma.2. The positive expression rates of CD 147, MMP-2 proteins and CD147 mRNA gradually increased with the increase of the papillary thyroid carcinoma size and lymph node metastasis. The expression of AnnexinⅡprotein gradually increased with lymph node metastasis. It indicates that the high expressions of CD147, MMP-2, AnnexinⅡproteins may be related with the further development of thyroid carcinoma and lymph node metastasis.3. There were high expressions of CD147, MMP-2, AnnexinⅡproteins in papillary thyroid carcinoma. And in the relationship of CD147, MMP-2 and AnnexinⅡproteins, the expression in papillary thyroid carcinoma between any two proteins were positively correlated. In addition, the co-expression of CD147, MMP-2, AnnexinⅡproteins closely related with the tumor size and lymph node metastasis. It suggests that these three proteins may play a synergistic effect in the occurrence, development and lymph node metastasis of papillary thyroid carcinoma.