Expression And Clinical Significance Of GLUT-1 And MMP-2 In The Tissue Of Human Malignant Ovarian Tumor

Objective:To study the expression of glucose transporter protein-1(GLUT-1) and matrix metalloproteinase-2(MMP-2) in the tissue of benign ,borderline and malignant ovarian tumor and to explore the correlation between the expression of GLUT-1 and MMP-2 and the malignant status,including clinical stage,histological types, differentiation,metastasis and prognosis. Methods:Random select 50 cases of ovarian tumor specimen,including 30 cases of human ovarian carcinomas,8 cases of human ovarian borderline ovarian tumors and 12 cases of benign ovarian tumors,which were divided into several groups according to histological types,clinical stage and differentiation. Immunohistochemistry was used to measure the expression of GLUT-1 and MMP-2 in these tissues of ovarian tumor.The data was statistically analyzed using Fisher's exact probabilities,analysis of variance,Spearman rank correlation and regression. Results:1.Age as a mixed factor was excluded(P﹥0.05). 2.The expression levels of GLUT-1 and MMP-2 in human borderline and malignant ovarian tumors were higher than those in human benign ovarian tumors with the difference being significant(P=0.0000004 ,0.0447).GLUT-1 was detected mainly in cytomembrane of tumor cell,and it can also be found in cytoplasm of tumor cell . MMP-2 could be detected both in cytoplasm and cytomemebrane of tumor cell.The color observed was yellow. 3.The expressions of GLUT-1 and MMP-2 are correlated with the clinical stage(P=0.014,0.009).No significant difference was found in the expressions of GLUT-1 and MMP-2 among the histological types(P=0.223,0.697) and differentiation(P=0.998,0.217). 4.The expression levels of GLUT-1 and MMP-2 in human malignant ovarian tumor with metastasis were higher,and the intensity of GLUT-1 expression was strong in most of malignant ovarian neoplasms with Ⅲ～Ⅳstages. GLUTs are glycoproteins in the cytomembrane,and play great roles in glycometabolism.GLUT-1 belongs to thisfamily.It is predominantly expressed in erythrocytes,CNS cells,placerta and fetal cells,but it has also been observed in various solid tumors.Tumor cells exhibit an enhanced glucose metabolism compared to benign tissue because they proliferate rapidly,and the key mechanism of enhanced glucose metabolism in carcinoma cells involves the overexpression of transmembrane glucose transporter proteins(GLUTs) especially GLUT-1. MMPs are zinc-dependent metalloproteinases,which are classified on the basis of their substrate specificities:collagenases,gelatinases, stromelysins and membrane-type MMPs .MMPs are asssociated with origin and development of ovarian tumors,such as MMP-2(72-KD, gelatinase A) has been linked to enhanced tumor invasion by degrading basement membrane and extracellular matrix. The aim of the present study was to analyze the expression of GLUT-1 and MMP-2 in the tissue of benign ,borderline and malignant ovarian tumor using immunohistochemistry.We found that GLUT-1 expression wasweak to negative in all benign ovarian neoplasms and moderate in most borderline tumors and moderate to strong in almost all ovarian cancers ,which suggested that increased glucose uptake and utilization is a major feature of malignant tumors.The expression rates of MMP-2 were gradually increased with the progress of ovarian lesions.Our study confirmed there was no significant difference in expressions of GLUT-1 and MMP-2 among the histological types and differentiation.In addition,we also found that GLUT-1 and MMP-2 overexpressions were associated with invasiveness.High GLUT-1 and MMP-2 expressions are associated with increased invasiveness and metastasis of tumor cells,but GLUT-1 overexpression was only associated with increase cellular proliferation and increase malignant potential.It has not been proved that the increased invasiveness and metastasis is by GLUT-1 overexpression alone because,to invade and metastasize,tumor cells must degrade basement membrane and extracellular matrix.These activities are carried outby MMPs especially MMP-2.There has been a report to show a statistically significant association between GLUT-1 and MMP-2 expression,and suppression of GLUT-1 expression by antisense oligonucleotides decreased MMP-2 expression and invasiveness,which support that GLUT-1 modulates MMP-2 expression,but we cannot exclude the possibility that there is other mechanisms.Suppression of GLUT-1 expression may be a new approach to suppressing the metastasis of ovarian cancer that overexpress GLUT-1.There is controversy about GLUT-1 overexpression and prognosis. This study suggested that high GLUT-1 expression indicated poor chemotherapy effect and poor prognosis,but sample size in this study was small and the unfollown-up rate was high,so we need more study to assure it. Conclusions:1. The expression levels of GLUT-1 and MMP-2 in human borderline and malignant ovarian tumors were higher than those in human benign ovarian tumors with significant difference ,and were associated with clinical...