Expressions Of MMP-2, MMP-9, TIMP-2, TIMP-1Non-melanoma Cell Carcinoma

ObjectiveSkin tumor is a kind of malignant tumor always involving with epidermis and skin appendages.It was mainly divided into melanoma skin cancer and non-melanoma cell carcinoma. Squamous Cell Carcinoma (SCC) and Basal Cell Carcinoma (BCC) are both common non-melanoma skin cancers in Plastic Surgery.They are often in face, neck and other long-term exposure skin of the body. SCC and BCC are both derived from the epidermis or skin adnexal keratinocyte skin cancer. The incidence of SCC and BCC is the damage result due to the accumulation of multiple genes and multiple steps.SCC and BCC are basal cell skin cancers of normal skin, which both have higher incidence in skin cancers. With the improvement of people’s living standard and the average life expectancy, the incidence of skin cancer is also increasing year by year. Skin cancer infiltration and transfer could affect the quality of life of the majority of patients and endanger the lives of some patients. Infiltration and invasion of skin tumors is an active process, which mainly consists of three steps:adhesion, degradation and transfer.Matrix Metalloproteinase (MMPs) is the main protein for degradation of extracellular matrix, which plays an important role in tumor invasion and metastasis. The key physiological function of matrix metalloproteinase protein is the degradation of variety ingredients of extracellular matrix (ECM) and the basement membrane (BM) in the neutral pH environment. Extracellular matrix and basement membrane are the main cell biological defenses, which could limit the invasion and metastasis of tumor cells. When they are constantly destroyed, it will lead that the surrounding normal tissue to be continually infiltrated by cancer cells. MMPs specific inhibitor is Tissu Inhibitor of Matrix Metalloproteinase (TIMPs), which inhibits the invasion and metastasis of tumor cell by down-regulating the degradation activity of metalloproteinases.In MMPs family, MMP-2and MMP-9are gelatinases of type IV collagenase. The main component of ECM and BM is type IV collagen. MMP-2and MMP-9as form of zymogen secreted into the ECM are activated to play a physiological role in decomposition of the type IV collagen and undermine the integrity of ECM. In addition to the integrity destruction of the extracellular matrix and basement membrane, and promoting invasion and metastasis of cancer cells, MMP-2and MMP-9could also promote angiogenesis in tumor.TIMP-2is a non-glycosylated protein whose molecular weight being21KD, TIMP-1is a glycosylated protein whose molecular weight being28KD. TIMP-2and TIMP-1are specific inhibitors of MMP-2and MMP-9, and plays a role in the inhibition of tumor invasion and metastasis. TIMP-2and TIMP-1combined with the activated MMP-2and MMP-9makes them lose activity, which plays an inhibitory effect in tumor invasion and metastasis.MMP-2, MMP-9, TIMP-2,TIMP-1all have higher expressions in many cancers of human being, but few research in SCC and BCC. There is also a dispute in this areas. This paper analyzes the expressions in non-melanoma skin cancer and its clinical significance of MMP-2,MMP-9and their inhibition factors TIMP-2, TIMP-1.It also describes the relationship in occurrence, development and transfer of matrix metalloproteinases and their inhibitors in skin tumor.Methods48cases of skin cancer surgical specimens were taken from Plastic Surgery of the First Affiliated Hospital of Zhengzhou University, with draw parts including head, neck, genitalia, extremities, trunk.They are26males and22females, whose age30to79years old. All patients did not have merge connective tissue disease or any disease of the immune system and vital organs.They skin cancer has no treatment of radiotherapy, immunotherapy, freezing and laser before surgery. There was no significant difference in patients’ gender, age, disease duration and lesion in each group. There are26cases of SCC (SCC group),22cases of BCC(BCC group)patients with pathologically confirmed.Diseased tissue was removed surgically, SP method was adopted for the immunohistochemical detection, then MMP-2, MMP-9and TIMP-2, TIMP-1positive expression rate, staining intensity and expression intensity in non-melanoma skin cancer were recorded. At the same time, the results were compared with the control group, and the factor expression differences were also compared in the SCC group, BCC group and control group. Results1. MMP-2and MMP-9are mainly expressed in basal cell and squamous cell membrane, some expression in the cytoplasm. The positive expression rates of basal cell carcinoma are86.4%,81.8%. The positive expression rates of squamous cell carcinoma are96.2%,92.3%. The positive expression rates of normal skin are30.0%,35.0%. Comparing the positive expression rates of non-melanoma skin cancer and normal skin tissue are statistically significant (P<0.05).2. TIMP-2and TIMP-1are mainly expressed in basal cell and squamous cell membrane, some expression in the cytoplasm. The positive expression rates of basal cell carcinoma are63.6%,68.2%. The positive expression rates of squamous cell carcinoma are61.5%,57.7%. The positive expression rates of normal skin are95.0%,100%. Comparing the positive expression rates of non-melanoma skin cancer and normal skin tissue are statistically significant (P<0.05).Conclusion1. High expressions of MMP-2and MMP-9in the non-pigmented skin cancer indicates that MMP-2and MMP-9are related to the development of non-melanoma skin cancer.2. TIMP-2, TIMP-1in non-melanoma cell carcinoma show low expressions, indicating that TIMP-2, TIMP-1inhibit the development of non-melanoma skin cancer. 3. MMPs is positively correlated with the invasion and metastasis of SCC and BCC, and TIMPs is negatively correlated with the infiltration and transfer of SCC and BCC, therefore it may play an important role in invasion and metastasis of NMSC.