| BackgroudCutaneous malignant melanoma (CMM) is a malignant tumor that is originated from the neural crest melanocytes cells.Due to many factors, the incidence of CMM tends to be increased year by year. CMM is prone to blood and lymph node metastasis, poor prognosis and high mortality.But a large number of experimental studies have confirmed that, like many other malignancies, the occurrence and development of CMM is an interaction process of multi-factor, multi-phase and multi-step. Early diagnosis and treatment can effectively control the occurrence and development of melanoma.The treatment of CMM has been diversifying in recent years,emphasizing on individual therapy and multidisciplinary treatment.Among these treatments,the gene targeted therapy against the invasion and metastasis of CMM has also become a future treatment direction.More and more studies shown that metastasis-associated gene1(MTAl) and T lymphoma invasion and metastasis inducing gene1(Tiaml) are closely related to the invasion and metastasis of many malignant tumors.The study has found that MTA1is a part of the NuRD (nucleosomeremodeling and histone deacetylase)complex.The NuRD composite can affect chromatin state,thereby regulating the replication of the gene. Another study has found that the functional areas of the MTA1contain a SH3-binding area.The residue sequence which is contained in SH3-binding region can pair with the SH3-binding domain of the Src gene.The SH3binding domains are related to the invasion and metastasis-related genes of signal transduction pathway,such as Tiaml. The study has found that Tiaml is a downstream effector factor of the Src gene. There is an interaction between Tiaml and MAPK pathway. Tiaml can activate p38MAPK pathway,and then the activation of p38can induce the expression of MMP-9.There is still no research about whether there is a connection among MTAl,Tiaml and MMP-9.The study about the connection of MTAl,Tiaml and the clinical pathological features of CMM is rarely reported. Now,in order to explore the invasion and metastasis mechanism of CMM and to find a new therapeutic target for the treatment of the CMM, we need some further investigations about MTA1and Tiaml.AimTo detect the expression of MTA1, Tiaml and MMP-9protein in cutaneous malignant melanoma,junction nevus and normal skin tissue.To investigate the connection between the expression of MTA1,Tiaml and MMP-9protein and the clinicopathological features of cutaneous malignant melanoma,as well as the interrelation among them.Method52cases of cutaneous malignant melanoma paraffin blocks and20cases of junction nevus paraffin blocks have been collected by the department of pathology in the First Affiliated Hospital of Zhengzhou University during2009～2012.All of these paraffin blocks have complete resection and clear pathological diagnosis. CMM patients include24males and28femals, aged22to76years old,and the average age is (56.8±11.2) years old.According to lymph node metastasis,they can be divided into two groups:18cases with lymph node metastasis,24cases without lymph node metastasis. According to the depth of tumor invasion by Clark classification scheme,they can be divided into five groups:Level I (epidermis and adnexal epithelium)14cases,Level Ⅱ-Ⅲ(papillary dermis)14cases,Level IV(reticular dermis)9cases,Level V (subcutaneous tissue)15cases.20cases of junction nevus:9cases are males and11cases are females, aged11-78years old, the average age is (53.5±10.3) years old.20cases of normal full-thickness skin tissue are chosen as control groups, which come from Plastic Surgery of the First Affiliated Hospital of Zhengzhou University surgery resection.12cases are males,8cases are females. Aged14to71years old.The average age is (52.8±11.1) years old. All of these people have complete medical history information and don’t have any other diseases. On the other hand, they don’t have any relevant treatments before surgery, such as laser treatment, radiation therapy, chemotherapy and so on. There is no significant difference in patients’gender, age, disease lesion and so on.They are comparable (P＞0.05).We use SP immunohistochemical technique to detect the expression of MTAl, Tiaml and MMP-9in cutaneous malignant melanoma of the52cases, skin junction nevus of the20cases and normal skin tissue in the20cases. The statistics data is processed by SPSS17.0software. We use the Chi-square test to compare the expression of MTAl, Tiaml and MMP-9protein. On the other hand, we analyze the relation between three proteins and tumor cell invasion and metastasis. We analyze the correlation of the expression of three proteins in CMM tissue by the Spearman rank correlation analysis method. The test standard is0.05and the standard of x2division is0.0167.Results1. The MTA1protein product are mainly expressed on the cytoplasm of cells, but it also expressed on some cell’nucleus.MTAl is highly expressed in the CMM. The positive expression rate in CMM is71.2%(37/52).The positive expression rate in the junction nevus and normal skin tissue is lower. The positive expression rate is40.0%(8/20) and30.0%(6/20).On the one hand,we have found that, with the depth of tumor infiltration increasing, the expression level of MTA1in CMM has increased (P＜0.05).On the other hand,we have found that the expression level of MTA1in the tissue with lymph node metastasis is significantly higher than that without lymph node metastasis (P<0.05).2. The Tiaml protein products are mainly expressed on the cytoplasm of cells. Tiaml is highly expressed in the CMM. The positive expression rate in CMM is76.9%(40/52).The positive expression rate in the junction nevus and normal skin tissue is lower. The positive expression rate is35.0%(7/20) and25.0%(5/20).On the one hand,we have found that,with the depth of tumor infiltration increasing, the expression level of Tiaml in CMM has increased (P＜0.05).On the other hand,we have found that the expression level of Tiaml in the tissue with lymph node metastasis is significantly higher than that without lymph node metastasis (P＜0.05).3. The MMP-9protein is mainly expressed on the cytoplasm of cells. MMP-9is highly expressed in the CMM. The positive expression rate in CMM is75.0%(39/52).The positive expression rate in the junction nevus and normal skin tissue is lower. The positive expression rate is40.0%(8/20) and30%(6/20).On the one hand,we have found that,with the depth of tumor infiltration increasing, the expression level of MMP-9in CMM has increased (P＜0.05).On the other hand,we have found that the expression level of MMP-9in the tissue with lymph node metastasis is significantly higher than that without lymph node metastasis (P＜0.05).4. The correlation analysis of MTAl,Tiaml and MMP-9has shown that the expression of MTA1and Tiaml in CMM is positively associated (rP=0.356,P=0.009,P＜0.05). The expression of Tiaml and MMP-9in CMM is positively associated (rP=0.422yP=0.002,P＜0.05). The expression of MTAl and MMP-9in CMM is positively associated (rP=0.515, P=0.000, P＜0.05).Conclusions1. The expression levels of MTA1,Tiaml and MMP-9in CMM are significantly higher than the expression levels of MTAl,Tiaml and MMP-9in the junction nevus and the normal skin tissue. On the other hand,the expression of MTA1,Tiaml and MMP-9in CMM tissue is related to the invasion depth of tumor and lymph node metastasis (P＜0.05).2. The expression of MTA1and Tiaml in CMM is positively associated. The expression of Tiaml and MMP-9in CMM is positively associated. The expression of MTA1and MMP-9in CMM is positively associated.In CMM,It’s speculated that there may be some existing relationship among MTAl,Tiaml and MMP-9in CMM. They work together to promote tumor invasion and metastasis. 3. MTA1, Tiaml and MMP-9in CMM play an important role in tumor invasion and metastasis. The joint detection of the expression of them in CMM may be expected to provide a reference to the invasion and metastasis of tumor and the assessment of prognosis. On the other hand, it may offer a new idea for the gene therapy of CMM. |
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