Expression Of Endothelial Cell Specific Molecule-1 In Gastrointestinal Stromal Tumor And Its Relations With Collagenases And Tissue Inhibitors Of Metalloproteinases

Background:Gastrointestinal stromal tumor (GIST) , one of the most common sarcoma of the alimentary tract, is considered as deriving from the interstitial cells of Cajal (ICCs). Presently, many scholars tend to classify GIST into four types: extremely low risk,low risk, moderate risk and high risk, which is on the basis of its invasive chanciness according to the the size and the degree of karyokinesis of tumors. The underlying molecular mechanisms that exist in the invasive chanciness of GIST is still unclear. But more and more attention was paid to the relation between tumor extracellular matrix and tumor invasive chanciness, including endothelial-cell-specific moelecule-1 (ESM-1), matrix metalloproteinases (MMPs) , and tissue inhabitors of metalloproteinasrs-1(TIMPs). Endothelial-cell-specific molecule 1 (ESM-1) is a recently identified human endothelial cell-specific molecule. Studies have demonstrated that the expression of ESM-1 is correlated with certain tumors, such as the origin and development of lung cancer and renal carcinoma. Positive correlation has been found between the expression of ESM-1 and the degree of tumor invasiveness and its multivessel . Matrix metalloproteinases (MMPs) is a big family of proteolytic enzymes , including collagenase, gelatinase and membrane-MMPs , of which collagenase is the most important . Numerous studies have shown that collagenase plays essential roles in the invasion and metastasis of tumor , in a way that it not only contributes to the degradation of the extracellular matrix but also to the tumor microenvironment maintainence and growth of tumor. TIMPs are the inhibitors of MMPs. which could suppress the activation of all collagenases. Whether there is the expression of ESM-1 in GIST, and whether ESM-1 is related to the character and biological behavior of tumour, and whether there is close relations between collagenases and TIMP-1, are still unknown and deserve further study. Objective:To detect the expression level of ESM-1,MMP-1,MMP-3 and TIMP-1 in GIST, and to analyze their relation to respective clinical pathology data. To study the expression of ESM-1 and probe its relation to collagenase and tissue inhibitive factor and to find theory basis for the indicator of tumor invasion for the sake of clinical treatment and prognosis.Methods: Tissue microarry was used to detected the expression of ESM-1, MMP-1,MMP-3 and TIMP-1 in 69 cases of GIST by immunohistochemistry. The relation of ESM-1 expression to the clinical pathologic data, collagenase and tissue inhibitive factor was investigated .Results:(1)The expression of ESM-1 in the gastrointestinal stromal tumor is diffusely distributed and ESM-1 is mainly positive in the cytoplasm. ESM-1 is expressed in 68 cases of the 69 cases and the expression rate reaches to 98.5% (68/69). Of the 68 cases 63 cases are strong positive with a high expression rate of 91.3% ( 63/69). Along with increased degree of malignant GIST , the expression of ESM-1 increases with statistical significance (P<0.05). (2)In the form of pathological morphology , compared with the expression level of ESM-1 in spindle cells there is a trend that ESM-1 expression level in epithelial cells increases but with no statistical significance. ( 3 ) The expression rate of MMP-1,MMP-3 and TIMP-1 in the gastrointestinal stromal tumor reaches to 89.9%, 89.9% and 84.1% respectively. And they are positively correlated with ESM-1 expression. Conclusions:(1)ESM-1 is widely expressed in the gastrointestinal stromal tumor (GIST) with a high rate , and is closely related with the biological behavior of GIST , which might be a potential indicator of biological behaviour of GIST. (2)There is also a wide expression of collagenase and tissue inhibitive factor in GIST and they are both relate to the biological behavior of GIST as ESM-1 .