The Relationship Between The Expression Of Cystatin C And Microvessel Density In Endometrial Adenocarcinoma

BackgroundIn recent years, the morbidity of endometrial carcinoma has the trend of increasing all around the world. In recent 10-20 years, the incidence of endometrial adenocarcinoma increases 2 times than that in early the 1970s, and patients are younger than before. Although in the past 10 years , Gynecologic oncology scholars had strong interests in the basis and clinical experiment of endometrial carcinoma, and studied for a long time. But so far, the precise mechanism of progression of endometrial carcinoma is not clear. Thus, to explore the mechanism and new therapy for endometrial carcinoma has important significance.Cystatin C is a nonglycosyalated basic protein and a member of type II superfamily of cysteine Proteinase inhibitor. It is produced at a constant rate by lysosomal in nearly all nucleated cells. The reports before were focused on the assessment of renal function. Recent studies have found that Cystatin C is related with the development of malignant tumor. But there have been no reviews about the relationship between Cystatin C and the progression of endometrial adenocarcinoma so far.The growth of tumor cells depends on the nutrition around. The solid tumor larger than 1mm~2 needs angiogenesis, and new vessels can give pathway to tumor cell metastasis. Angiogenesis of endometrial adenocarcinoma is the main factor to improve the progression of tumor, and it is associated with tumor expansion and invasion. Microvessel density is an important target to measure tumor angiogenesis. We usually use anti-CD34 monoclonal antibody to tag the microvessel in matrix. After immunohistochemistry, microvessel density can be observed under the microscope. The report about microvessel density in endometrial adenocarcinoma is little.The key step of tumor metastasis is that tumor cells invade into vessels or lymph system, and then grow in other organs. Tumor invasion and metastasis depend on the degradation of extracellular matrix and angiogenesis. Cathepsin can degrade the components of basement membrane and matrix protein(collagen,laminin and fiber etc), which is crucial to matastatic process. The recent study revealed that cathepsin is associated with not only the migration of tumor cells, but also angiogenesis. Cystatin C is the most important inhibitor of cathepsin. It can inhibit cathepsin's degradation activities, reduce its damage to tumor matrix and basement membrane, and decrease vessel growth factors, so as to control tumor angiogenesis and resist tumor invasion and metastasis. These were reported in breast cancer and colon cancer. But in endometrial adneocarcinoma, the inhibition role of Cystatin C to the migration of tumor cell, and the correlation between the expression of Cystatin C and microvessel density is worth to be studied.In our study, the expression of Cyatatin C and microvessel density in endometrial adneocarcinoma was detected by immunohistochemical method. The role of Cyatatin C in the development of endometrial adenocarcinoma and the relationship between Cystatin C and microvessel density were analyzed.ObjectiveThe aim of this study is to detect the expression of Cystatin C and microvessel density in endometrial adenocarcinoma , to explore the role of Cystatin C and its relationship with microvessel density in endometrial adenocarcinoma.MethodsWe collected 60 cases of endometrial adenocarcinoma which were diagnosed by pathology and no radiotherapy, chemotherapy and hormone therapy were given before the operation from August 2002 to November 2006. In accordance with FIGO1988, stageI:22 cases, stageII:14 cases, stageIII:15 cases,stageIV:9 cases. We also collected 30 cases of endometrial hyperplasia and 30 cases of normal endometrium for controls during the same period. The pathological types of endometrial hyperplasia were as below: 6 cases of simple hyperplasia, 9 cases of complex hyperplasia and 15 cases of atypical hyperplasia. All of the samples were embedded in paraffin, and continuous sliced 3 times, the thickness is 4μm, and then stained by HE and immunohistochemical method. Envision immunohistochemical method was used to detect the expression of Cystatin C and CD34 in three different types of endometrium tissue. By Weidner' s method, the microvessel density can be counted in different types of endometrium tissue.Results1. In endometrial adenocarcinoma, total positive expression rate of Cystatin C was 61.67%. Positive expression rates of Cystatin C in stage I, stage II, stage III and stage IV were 63.64%, 57.14%, 53.33% and 77.78%. Although there was decreasing trend with increasing stages,there was no statistics difference within different stages(P=0.745). There was no significant difference of the expression of Cystatin C within different types of endometrial hyperplasia (P=0.084) , but the expression of Cystatin C in atypical hyperplasia was lower than that in simple hyperplasia (P = 0.032) . From normal endometrium, endometrial hyperplasia to endometrial adenocarcinoma, the expression of Cystatin C was gradually decreasing (positive rates: 83.33%> 73.33%>61.67%), but there was no significant difference (P=0.134) .2. In endometrial adenocarcinoma, total median MVD was 66.50, total mean MVD was 66.58. Median MVD of stage I,stage II,stage III and stage IV was 56.00, 65.84, 71.33and 82.00; Mean MVD was 57.44, 64.83, 73.07 and 80.85. With the increasing stages, microvessel density was gradually increasing (P=0.001) . There was significant difference within different types of endometrial hyperplasia (P=0.035) . From normal endometrium, endometrial hyperplasia to endometrial adenocarcinoma, microvessel density was gradually increasing (median MVD: 29.67<57.34<66.50), and there was significant statistics difference within these three groups (P=0.000) .3. In endometrial adenocarcinoma, there was correlation between Cystatin C and microvessel density (P=0.012). Excepting for these factors such as stages and pathologic grades, there was no correlation between the expression of Cystatin C and microvessel density (R=-0.197, P=0.132) . But if these factors such as stages and pathologic grades were included, there was moderate inverse relation between the expression of Cystatin C and microvessel density (R=-0.3002, P =0.022) . There was no correlation between the expression of Cystatin C and microvessel density in endometrial hyperplasia (P=0.788) .Whether factors such as pathologic types were included or not,no correlation was found (R=-0.0087, P=0.964; R=-0.210, P= 0.265) . In normal endometrium, there was significant correlation between Cystatin C and microvessel density (P=0.002) , and there was high inverse relation (R=-0.694, P =0.000) .Conclusions1. From normal endometrium, endometrial hyperplasia to endometrial adenocarcinoma, there was no significant statistics difference in the expression of Cystatin C, which suggests that Cystatin C may not play the main role in the progression of endometrial adenocarcinoma.2,From normal endometrium, endometrial hyperplasia to endometrial adenocarcinoma, microvessel density is gradually raising, and with the increasing stages of endometrial adenocarcinoma, microvessel density is gradually raising, which suggests that angiogenesis may play an important role in the progression of endometrial adenocarcinoma.3,There was moderate inverse relation between the expression of Cystatin C and microvessel density, which suggests that Cystatin C may be involved in the regulation of tumor angiogenesis.