Expression And Significance Of S100A4, E-cadherin And Heparanase In Malignant Melanoma

The most importement and most essential biology characteristic of malignant tumors are invasion and metastasis. They are also the main reason of the sufferers' death or badly prognosis. It has been proved that many special genes play important parts in the invasion and metastasis of malignant tumors. Malignant melanoma is a relatively common and highly malignant tumor which derived from melanocytes. It has the character of development quickly, transfer easily, prognosis badly, highly death rate. Data displays that the incidence rate of melanoma is the third one in the cutaneous malignant tumors(6.8%～20%).Currently, the position of the malignant melanoma inside the scope of the world is the very rigorous. The mission of control and lower the incidence of the malignant melanoma is terribly difficult and huge.The recently molecular biology studies show that many genes have emerged as important roles with the capacity to promote invasion and metastasis of many human neoplasms. Recent studies shed light on the mechanisms of action of protein S100A4, and indicate its possible prognostic role in human neoplasms by an analysis of online serial analysis of gene expression (SAGE) database. In order to clarify the molecular mechanism of human malignant melanoma, we collected specimens from melanoma,melanocytic nevus and normal skin tissues. The SP immunohistochemical method was used to detect the expression of S100A4, E-cadherin and heparanase in 30 cases of malignant melanoma, 30 cases of melanocytic nevus and 15 cases of normal skin tissues. It will provide theoretic basis for tumorigenesis mechanism and therapy.Materials and methords75 case of paraffin wax embedded samples were available from the First Affiliated Hospital of Zhengzhou University. Of them 15 were normal skin tissues, 30 were melanocytic nevus and 30 were malignant melanoma tissues. To elucidate the involvement of S100A4, E- cadherin and heparanase in malignant melanoma,we using monoclonal antibodies against E-cad, HPSE and polyclonal antibodies against S100A4 to examined expression of the protein by immunohistochemistry. Statistical analysis was performed by the SPSS10.0 software package. Differences among group were analyzed by using analysis of the Chi-squared test and Person Correlation. All of the P values resulted from tow-side statistical test. Satistically significant level was considered as "alpha equals 0.05"(a=0.05)Results1. The expression of S100A4 was negative in the normal skin tissue; 13.33%(4/30) in melanocytic nevus ;it was detectable in cytoplasm or/and membrance in the malignant melanoma tissues. The positive expression rate of S100A4 was 66.67% (20/30) in malignant melanoma tissues. There were significant differences between malignant melanoma and melanocytic nevus or normal group(x₁²=17.778, P=0.000; x₂²=18.000, P=0.000) .2. The positive immunostaining rate of E-cadherin in normal, melanocytic nevus and malignant melanoma were 100%(15/15),83.3% (25/30) and 43.33% (13/30) respectively. There were significant differences between malignant melanoma and melanocytic nevus or normal group (x₁²=10.335, P=0.001; x₂²=13.661, P=0.000) .3. The positive immunostaining rate of HPSE in normal skin tissue,melanocytic nevus and malignant melanoma were 6.67%(2/30) and 63.33 % (19/30) respectively. There were significant differences between malignant melanoma and melanocytic nevus or normal group(x₁²=21.172, P=0.000; x₂⁼16.442, P=0.000). 4. The expression of S100A4 positively correlated with the lymph node metastases (P<0.05);E-cadherin expression correlated with lymph noda metastases (P<0.05); HPSE expression correlated with lymph node metastases a (P<0.05).5. The expression of S100A4 correlated to E-cadherin and HPSE in malignant melanoma (the coefficient are r=-0.523, r= 0.506,P<0.05); the expression of HPSE positively correlated to E-cadherin in malignant melanoma (r=-0.451, P<0.05).Conclusions1. In malignant melanoma, over expression of S100A4 indicated that there was a close relationship between S100A4 and the cancer progression. The expression of S100A4 positively correlated with the clinical stages and lymph node metastases, indicated that there was a close relationship between S100A4 and the invasion and metastasis of malignant melanoma.2. In malignant melanoma, the expression of E-cadherin correlated with the lymph node metastases and the differentiation of tumor, indicated that there was a close relationship between it and the metastasis and the malignant progress. It could be useful markers for malignancy and metastasis of malignant melanoma.3. In malignant melanoma, over expression of HPSE indicated that there was a close relationship between HPSE and the cancer progression. The expression of HPSE positively correlated with the clinical stages and lymph node metastases, ndicated that there was a close relationship between HPSE and the invasion and metastasis of malignant melanoma.4. The expression of S100A4 negatively correlated to E-cadherin and HPSE in malignant melanoma. It indicated that they had different roles in the progression, invasive and metastasis of the malignant melanoma.