Expression Of S100A4, MMP-2 And TIMP-2 In Gastric Cancer And Their Clinical Significance

Objectives:S100A4,a member of S100 family of Ca²⁺-binding proteins,displays elevated expression in malignant human tumors compared with benign tumors,and increased expression correlates strongly with poor patient survival.Matrix metalloproteinases(MMPs) and their inhibitors(TIMPs)play a major role in the maintenance of extracellular matrix homeostasis.Alterations of MMPs and TIMPs expressions have been found in several malignant tumor entities.S100A4,MMP-2 and TIMP-2 may play a pivotal role in invasion and metestasis of malignant tumors.In this study,the exprsssion of S100A4,MMP-2 and TIMP-2 were investigated at protein levels in gastric cancinoma to examine the association with tumor invasion and metastasis of stomach neoplasm.Methods:From January 2006 through July 2007,fourty-nine randomly selected patients'(45 male,4 female)paraffin samples who underwent radical tumour nuphrectomy in Jinan Center Hospital were included in our study with diagnosed gastric cancer.The mean age was 61.55 years(range from 40 to 81 years).All patients weren't under radiotherapy and chemotherapy who were summarized in Tableâ… .At the same time,we collected 20 normal gastric mucosa tissues as Tableâ…¡.The expressions of S100A4,MMP-2 and TIMP-2 were detected by SP immunohistochemstry method in 49 cases of gastric cancer tissue and 20 cases of normal gastric mucosa tissue.The correlations of S100A4,MMP-2 and TIMP-2 to clinicopathologic features were analyzed.The investigators were blinded to information on immunostaining until conclusion of this study.We compared the differences between the two teams to explore their functions in tumor metastasis and infiltration.Results:1.The positive rate of S100A4 was 59.18%was higher significantly in gastric cancer in normal stomach tissues(0.00%)(p＜0.05).The expression rates of MMP-2(67.35%) and TIMP-2(77.55%)were also significantly higher in gastric cancer tissues than in normal stomach tissues(20.00%;20.00%)(p＜0.05;p＜0.05).2.The expression rate of S100A4 was increased significantly in stageâ…¢-â…£than in stageâ… -â…¡in gastric cancer(93.33%vs 44.12%,p=0.001).The positive rate of S100A4 was signifantly higher in gastric cancer tissues with lymphatic metastasis than in stomach neoplasm tissues without lymphatic metastasis(82.35%vs.6.00%, p=0.000).The expression of S100A4 was closely related to the TNM stage(r=0.710, p=0.000)and lymphatic metastasis(r=0.620,p=0.000).Meanwhile,the expression rate of S100A4 was increased significantly with depth of tumor infiltration(r=0.420, p=0.003).There was no correlation between the expression of S100A4 and age,gender, differentiation and histotypes(p＞0.05).3.The positive rate of MMP-2 was higher significantly in stageâ…¢-â…£than in stageâ… -â…¡in gastric cancer(100%vs 52.94%,p=0.001).The positive rate of MMP-2 was signifantly higher in gastric cancer tissues with lymphatic metastasis than the ones without lymphatic metastasis(82.35%vs.33.33%,p=0.000).The expression of MMP-2 was positive associated with the TNM stage and lymphatic metastasis(r=0.555,p=0.000; r=0.482,p=0.000,respectively).Meanwhile,the expression of MMP-2 was increased obviously with depth of tumor infiltration(r=0.420,p=0.003).No correlations was found between the expression of MMP-2 and age,gender,differentiation and histotype in stomach neoplasm(p＞0.05).4.There was no obvious differences between the TNM stage,lymphatic metastasis and depth of infiltration(p＞0.05).Also,no positive correlation was found between the expression of TIMP-2 and age,gender,differentiation and histotypes of gastric cancer(p＞0.05).5.The expression of S100A4 in gastric cancer was correlated with that of MMP-2 (r=0.572,p=0.000),while the expression of TIMP-2 was not correlated with that of S100A4 and MMP-2(r=0.051,p＞0.05;r=0.043,p＞0.05,respectively).Conclusions:S100A4 and MMP-2 play a critical role in tumor metastasis.By contrast,the abnormal expression of TIMP-2 and its function of inhibiting tumor infiltration and migration needs further investigation.Co-detection of expression of S100A4 and MMP-2 can be used to evaluate high metastasis potential of gastric cancer.