Expressions And Clinical Significance Of AnnexinⅡ,S100A4 And VEGF-C In Papillary Thyroid Carcinoma

Objective:Tumor development, invasion and metastasis are extremely complex processes of multi-factors, multi-step. AnnexinⅡis a calcium-mediated phospholipid binding protein family, participate in a series depends on the calcium ion membrane biological functions. AnnexinⅡcan accelerate DNA replication and regulate cell cycle to promote tumor cell proliferation, through participation in fibrinolysis, cell adhesion to promote tumor metastasis, play an important role in tumor occurrence development,invasion and metastasis. S100A4 protein is a calcium binding protein, can through several aspects such as increase the exercise capacity of tumor cells, reduce the adhesion between tumor cells and promote angiogenesis, promote extracellular matrix degradation and remodeling to promote tumor metastasis. Vascular endothelial growth factor C is a new members of human vascular endothelial growth factor family, also known as lymphatic endothelial growth factor.It through binding receptor VEGFR-2, VEGFR-3 to autophosphorylation and stimulate the proliferation of lymphatic endothelial cells and regulate tumor angiogenesis, promote tumor cells into the lymphatic and spread to the body lymphatic system and transfer. In this study, the immunohistochemistry and in situ hybridization technique was used to test the different expressions of calcium phospholipid binding proteinⅡ(AnnexinⅡ), calcium-binding protein S100A4 and vascular endothelial growth factor C (VEGF-C) proteins and AnnexinⅡmRNA in tissues of 50 papillary thyroid carcinoma,14 thyroid adenoma,26nodular goiter and 10 normal thyroid gland,and investigate its relationship with the development of thyroid papillary carcinoma and lymph node metastasis, and the relevance of the three.Method:The immunohistochemistry S-P and in situ hybridization technique was used to test the different expressions of AnnexinⅡ,S100A4, VEGF-C proteins and AnnexinⅡmRNA in tissues of 50 papillary thyroid carcinoma,14 thyroid adenoma, 26nodular goiter and 10 normal thyroid gland.Results:1. The positive expression rate of AnnexinⅡprotein in papillary thyroid carcinoma tissues was 82.00%(41/50), in hyroid adenoma tissues was14.29%(2/14) and in nodular goiter tissues was7.69%(2/26);whilewas negative in all of the normal thyroid tissues. The positive expression rate in papillary thyroid carcinoma tissues was higher than that in hyroid adenoma tissues (P<0.05), the positive expression rate was higher than that in nodular goiter.Positive rate of AnnexinⅡwere 100% (21/21) in lymph node positive groupand 68.97%(20/29) in lymph node negative group.There was significant difference between the 2groups (P<0.05). Annexin II expression was not correlated with sex,age and carcinoma size.2. The positive expression rate of S100A4 protein in papillary thyroid carcinoma tissues was 78.00% (39/50), in hyroid adenoma tissues was28.57 (4/14) and in nodular goiter tissues was3.85%(1/26);whilewas negative in all of the normal thyroid tissues. The positive expression rate in papillary thyroid carcinoma tissues was higher than that in hyroid adenoma tissues (P<0.05), the positive expression rate was higher than that in nodular goiter.Positive rate of S100A4 were95.24%(20/21) in lymph node positive groupand 65.52%(19/29) in lymph node negative group.There was significant difference between the 2groups (P<0.05). S100A4 expression was not correlated with sex,age and carcinoma size.3. The positive expression rate of VEGF-C protein in papillary thyroid carcinoma tissues was 76.00%(38/50), in hyroid adenoma tissues was35.71%(5/14) and in nodular goiter tissues was7.69%(2/26);whilewas negative in all of the normal thyroid tissues. The positive expression rate in papillary thyroid carcinoma tissues was higher than that in hyroid adenoma tissues (P<0.05), the positive expression rate was higher than that in nodular goiter.Positive rate of VEGF-C were95.24%(20/21) in lymph node positive groupand 62.07%(18/29) in lymph node negative group.There was significant difference between the 2groups (P<0.05) VEGF-C expression was not correlated with sex,age and carcinoma size.4. The positive expression rate of AnnexinⅡmRNA protein in papillary thyroid carcinoma tissues was 74.00%(37/50), in hyroid adenoma tissues was14.29%(2/14) and in nodular goiter tissues was3.85%(1/26);while was negative in all of the normal thyroid tissues. The positive expression rate in papillary thyroid carcinoma tissues was higher than that in hyroid adenoma tissues (P<0.05), the positive expression rate was higher than that in nodular goiter.Positive rate of AnnexinⅡmRNAwere90.48%(19/21) in lymph node positive groupand 62.07%(18/29)in lymph node negative group.There was significant difference between the 2groups (P<0. 05). AnnexinⅡmRNA expression was not correlated with sex,age and carcinoma size.5. In papillary thyroid carcinoma, the expressions of AnnexinⅡprotein and S100A4, VEGF-C proteins were positively correlated; the expressions of S100A4 protein and VEGF-C protein were positively correlated(P< 0.05); the expressions of AnnexinⅡprotein and AnnexinⅡmRNA were positively correlated.Conclusion:1. AnnexinⅡprotein, S100A4 protein and VEGF-C protein in normal thyroid tissues, nodular goiter tissues and hyroid adenoma tissues is no expression or low expresseion,but in papillary thyroid carcinoma tissues is high expression,it implies that AnnexinⅡprotein, S100A4 protein and VEGF-C protein related to the occurrence of papillary thyroid carcinoma.2. The positive expression rate of AnnexinⅡprotein, S100A4 protein and VEGF-C protein in the lymph node metastasis group were higher than that in nonlymph node metastasis group, respectively,a significant difference between them,which indicate that the high expression of AnnexinⅡprotein, S100A4 protein and VEGF-C protein may promote the invasion and metastasis of papillary thyroid carcinoma.3. The expressions of AnnexinⅡprotein and AnnexinⅡmRNA were positively correlated,and the positive expression rate of Annexin II protein was higher than AnnexinⅡmRNA in papillary thyroid carcinoma, which indicate that the high expression of Annexin II protein have a positive correalation with the high transcription activity of mRNA.4. In papillary thyroid carcinoma,the expression of AnnexinⅡprotein, S100A4 protein,VEGF-C protein and AnnexinⅡmRNA was positively correlated,it implies they have certain synergy to promote invasion and lymph node metastasis of papillary thyroid carcinoma,participate in tumor invasion and metastasis.