Study On The Expression Of ESM-1and Its Correlation With VEGF, MVD, And Clinical Parameters In The Bladder Urothelial Carcinoma

Objective:Bladder cancer(BCa) is the most common urinary system malignancy，andits incidence increases annually. It is one of the most deadly urological tumors worldwide,with extremely variable prognosis, unknown pathogenesis or molecular basis ofdevelopment. In this study, the expression of human endothelial molecule-1(ESM-1) andthe relations between ESM-1expression and clinicopathological parameters in bladderurothelial carcinoma(BUC) tissues and the role of ESM-1in angiogenesis wereinvestigated, to study the action of ESM-1in carcinogenesis，invasion and metastasis oftumor.Methods and materials: ESM-1and VEGF expression and microvesseldensity(MVD) in95specimens of bladder urothelial carcinoma was measured by themethod of immunohistochemistry. cytoplasmic and/or nucleus immunostaining in tumorcells were considered positive. Positive reactions were scored for both intensity of stainingand percentage of positive cells. Intensity grades were0(no staining), l(weak staining, lightyellow),2(moderate staining, yellowish brown), to3(strong staining, brown)；percentagesof positive cells were scored as0(≤5%),1(6%~25%),2(26%~50%),3(51%~75%)4(≥76%).Scores of each sample were multiplied. We regarded “≥8” as high expression, scores of“4-7” as “middle expression” and scores of “2-3” as “low expression", while scores of“0-1” were considered “negative”. Cell ratio>10%of VEGF expression was consideredpositive. the MVD was defined by expression of CD34. The relationship between ESM-1expression and clinicopathological parameters, VEGF and MVD of bladder carcinoma wasanalyzed by χ2test, ANOVA and Spearman’s rank correlation analysis.Results:(1) cytoplasmic and/or nucleus immunostaining was stained in tumor cells. Inthe BUC, there were90cases with expression of ESM-1protein, the rate was94.7%，whilethere were only9.43%in the adjacent normal tissues, there were significant difference between them(P<0.01). ESM-1expression in cancer tissues was significantly higher thanin adjacent normal tissues.(2) ESM-1expression in BUC was positively correlated withhistological grade(G1:78.6%(11/14)/G2:96.8%(61/63)/G3:100%(18/18), clinical stage(Ta,T1:89.9%(62/67)/T2-T4:100%(28/28), lymph node metastasis(negative:71.4%(5/7)/positive:100%(6/6) and relapse(negative:92.5%(62/67)/positive:100%(28/28). There wasnot correlation between ESM-1expression and age/gender or the number and size of tumor.ESM-1expression of relapse of BUC was significantly higher than the initial issuance ofBUC,and there were significant differences(high expression rate ofprimary:50.0%(14/28)/relapse:75.0%(21/28).(3) By Spearman test, ESM-1and VEGFexpression of bladder urothelial cancer was significantly positively correlated (P<0.01).(4)By ANOVA analysis, ESM-1expression and MVD was significantly positively correlated(P<0.01).Conclusion:By immunohistochemistry, the study showed that ESM-1may play a roleas an oncogene during the tumorigenesis and development of BUC, its abnormal proteinexpression was closely related to clinical pathology, VEGF and MVD and may beassociated with the disordered regulations．Therefore, abnormal expression of ESM-1protein may suggest that the ESM-l involved in the carcinogenesis, growth, invasion andmetastasis of bladder urothelial cancer. ESM-l may serve as a biomarker of BUC andprovide us a new potential target for therapy.