Expression Of S100A4, E-cadherin And Nm23 In Thyroid Carcinoma And The Correlation With Lymphatic Metastasis

Background and objectiveThe incidence of thyroid carcinoma is increasing in the world. It is worthy to study the mechanism of development and metastasis of thyroid carcinoma. The S100A4 has been recently found as an important protein with the capacity of promoting malignant proliferate, invasion and metastasis of many human tumors. E-cadherin, a calcium-dependent cell-cell adhesion molecule, acts as maintenance of epithelial integrity. nm23 (non-metastatic 23) is an important tumor inhibit protein. Over expression of S100A4 protein,loss or dysfunction of E-cadherin and nm23 protein have been regarded as a malignant phenotype of tumor and play different roles on tumor development and metastasis. In this study, we use immunohistochemistry and image analysis technique to test the expression of S100A4, E-cadherin and nm23 in different thyroid tissue to investigate the relationship between the expression of these three proteins and development and metastasis of thyroid carcinoma.Materials and methodsThyroid tumor specimens: 166 specimens were obtained from patients who underwent biopsy for thyroid disease at Tumor Hospital of Shantou University Medical College from 1998 to 2007. There were 25 cases of benign multimodal goiters(MNG), 25 cases of Follicular adenoma, 61 cases of Papillary thyroid carcinoma(PTC) and 30 cases matched samples of adjacent normal thyroid tissue (N), 15 cases of Follicular thyroid carcinoma(FTC), 10 case of Medullar thyroid carcinoma(MTC),5 cases normal thyroid tissue. All the specimens were confirmed by pathologist.HE stain: Cell morphology was observed by light microscope after HE stains. Immunohistochemistry analysis: The Envision Labelled Peroxidase System two steps method were performed in the study. Immunohistochemistry (IHC) straining of S100A4, E-cadherin and nm23 was performed by standard techniques. The positive cells were counted by Leica Qwin4.0. MOD was determined by Image-Pro ? Plus 6.0. Result1. The expression of S100A4 protein was negative in all of the matched adjacent normal thyroid samples of carcinoma. The positive expression rate of S100A4 protein in Simple benign multimodal goiters,Follicular adenoma and thyroid carcinoma was increase gradually. The positive expression rate in thyroid carcinoma was much higher than that in the others(P<0.05), and Follicular adenoma and the matched adjacent normal thyroid samples of carcinoma have significant difference(P<0.05). There was significant difference between the others (P>0.05). The expression of S100A4 protein in thyroid carcinoma, the differences has statistical significance as follow: histological type,clinical TNM stage,lymph nodes metastasis(P<0.05). the differences has no statistical significance involved: sex,age and tumor size(P>0.05).The expression of S100A4 in matched lymph node metastasis tumor tissues was higher than its primary Thyroid carcinoma (P<0.05).2. The positive expression rate of E-cadherin protein in the matched adjacent normal thyroid samples of carcinoma, Simple benign multimodal goiters, Follicular adenoma and thyroid carcinoma was 93.3%,84.0%,80.0%和57.0%, respectively. The positive expression rate in thyroid carcinoma was lower than that in the others (P<0.05), Follicular adenoma and the matched adjacent normal thyroid samples of carcinoma had significant difference(P<0.05), and there was significant difference between the others (P>0.05). The expression of E-cad in thyroid carcinoma, the differences had statistical significance as follow: tumor size, histological type,lymph nodes metastasis(P<0.05). The differences had no statistical significance involved: sex,age and clinical TNM stage(P>0.05).The expression of E-cadherin in matched lymph node metastasis tumor tissues was not lower than its primary Thyroid carcinoma (P>0.05).3. The positive expression rate of nm23 protein in the matched adjacent normal thyroid samples of carcinoma,Simple benign multimodal goiters,Follicular adenoma and thyroid carcinoma was descent gradually. The positive expression in thyroid carcinoma was much lower than that in the others (P<0.05). The expression of nm23 in thyroid carcinoma, the differences has no statistical significance in the all the clinicopathological parameters (P>0.05). Positive rates of nm23 between the cases of primary tumors and their matched lymph node metastasis have no significant difference, too (P>0.05).4. The relationship of the expression of S100A4,nm23 and E-cad was analyzed by statistics, results showed that the former was negative correlation with the both later (rs=-0.274,rs=-0.252,P<0.05)and there was a positive correlation between later both(rs=0.284,P<0.05).Conclusion1. The expression of S100A4 protein in thyroid benign lesion and tumor,thyroid carcinoma is increasing,which may be closely related to the development of thyroid carcinoma.2. Positive rate of S100A4 in the cases of lymph node positive group was higher than that of lymph node negative group, and the expression of S100A4 in matched lymph node metastasis tumor tissues was higher than its primary Thyroid carcinoma .Over expression of S100A4 protein might be provided some useful information for invasion and metastasis of thyroid carcinoma.3. Loss or dysfunction of E-cadherin may be related to the metastasis of thyroid carcinoma. However the unusual expression of nm23 was not significant relate to metastasis of thyroid carcinoma.4. The expression of S100A4,E-cad and nm23 showed that the former was negative correlation with the both later and there was a positive correlation between later both. It is indicated that they could cooperate in the invasion and metastasis of thyroid carcinoma.