Expression Of Endothelin-1 In Bladder Carcinoma And Its Relationship With Microvessel Density

Objective:Bladder cancer is the most popular malignant tumor in urinary system,and transitional cell carcinoma (TCC) is the most common pathological type of it. Histopathological grade and stage are still the most important indexes to predict tumor recurrence and prognosis. However,tumor stage and grade may lead clinician to a wrong way sometimes because of the biological heterogeneity of bladder TCC. In fact, finding independent of the tumor grade, stage, while effectively guiding the assessment of tumor markers in the prognosis of work has been non-stop. Synthesis of tumor cells by certain protein can be used as tumor markers in the tumor and the diagnosis, treatment and prognosis are important reference value. Some or a tumor marker expression in the tumor or the expression of some of the tumor biology of important significance of the forecast. First, in invasive tumor tumor tissue damage close to the organization, which may occur before the transfer. If found a tumor marker to predict tumor cell invasion and metastatic level. Treatment and prognosis will have a significant impact. If the advance of the same tumor resistance to chemotherapy drugs forecast, the choice of treatment be of tremendous benefit. Most of the studies about Endothelin-1(ET-1),which has been proved to be an angiogenic factor,showed correlation with tumor grade,relapse and prognosis in bladder TCC. But the relationship of ET-1 with tumor angiogenesis and invasion is still unknown.In this study, 54 patients with bladder transitional cell carcinoma and 13 patients with normal bladder mucosa of the paraffin sections using immunohistochemical methods detected endothelin-1 (Endothelin-1, ET-1) and vascular endothelial expression of cell surface antigens CD34 MVD of monoclonal antibody markers to explore ET-1 and MVD in the development of bladder cancer, as well as the role of clinical significance.Methods: Tumor tissue from patients we chose with primary bladder TCC 54 cases from the Second Affiliated Hospital of Hebei Medical University urology between 2006-2008, including 47 cases of men and 7 women, aged 36-79 years, with an average age of 67.5; Aged≥60 years of age 39, <60 years of age in 19 cases; 40 Specimens were obtained from TURBt 5 from partial cystectomy and 9 from radical cystectomy. Among these specimens,18 were single tumors and 36 multiple ones,beginning of the 35 cases, 19 cases of recurrence. Tumor classification according to WHO standards: G₁-23 cases , G₂-21 cases , G₃-10 cases . Clinical staging by UICC criteria: Tis-T₁ for 33 cases , 18 cases for T₂ , T₃ for the two cases , one case of the T₄. 1₃ cases of normal tissues , from patients with no bladder TCC, all male , aged 23-74 years, with an average age of 61.4. SP immunohistochemical staining detected in normal tissues and bladder TCC in endothelin-1 (ET-1) expression and microvessel density (MVD) distribution.According to the results criteria: ET-1 results found in the cytoplasm or nucleus dyed brown or Sepia positive signs were positive results in the percentage of cells staining intensity of the Composite divided into qualitative analysis. High-power microscope observation of five random vision, vision each count 100 cells, the positive rate calculation: <25% for 0 , 25% -50% for 1 , 51% -75% for 2 , >75% for 3 ; by cell color and stained-depth: no Color 0 points, 1 Jianzong , yellow- brown 2 , Sepia 3 . Add two points < 2 is divided into negative, 2 - 3 is divided into weakly positive , 4 - 5 into positive .MVD's criteria:CD34 to vascular endothelial cells stained yellow or brown positive. First in low times microscope (100×) looking for high vascular density area, and then high power field (200×) count the number of microvessels. To the surrounding tumor cells and connective tissue components of any clear distinction between a vessel count, recording five in the number of capillary vision, choose the average value of MVD as a disease.All the experimental data were used SPSS13.0 version of statistical analysis software package. Counting related statistical information using chi-square test, measurement data related statistics by t-test, ET-1 expression and MVD calculated the correlation between using Spearman 'correlation analysis.Results:1 ET-1 expression:in the normal bladder and bladder cancer tissues, the positive rates were 7.7%, 53.7% difference was statistically significant (P <0.05); ET-1 levels in bladder cancer G₁, G₂, G₃-positive expression rates were 52.2%, 57.2%, 70%, the positive rate of grade G₁ 52.2% lower than the grade G₂, G₃, and the 61.3% level, the difference was significant (P <0.05). Invasive bladder cancer (T₂-T₄) and superficial bladder cancer (Tis-T₁) expression of the ET-1-positive rates were 57.2% and 51.5%, and there is a significant difference (P <0.05); Single bladder cancer, bladder cancer and many of ET-1 expression in positive rates were 44.5% and 58.3%, the difference was not significant early recurrence of bladder cancer and bladder cancer ET-1 expression in positive rates were 45.7% and 68.4%, and there is a significant difference (P <0.05); aged≥60 years and <60-year-old ET-1 expression in positive rates were 51.2% and 60.0%, and there is no difference.2 In the normal bladder mucosa of MVD (17.4±4.5), bladder cancer organizations of the MVD value (34.3±9.5), both compared to MVD in bladder cancer was significantly higher than that in the distribution of normal bladder mucosa (P <0.05). Grade G₁, G₂ and bladder tumor grade G₃ MVD respectively (31.2±5.1) (30.0±7.1) (50.3±2.8) compared between grade G₁, G₂ not obvious difference between class and class G₃ MVD was significantly higher than that of the grade G₁, G₂ level; Invasive bladder cancer (T₂-T₄) and superficial bladder cancer (Tis-T₁) MVD respectively (40.3±11.4) (30.4±5.5) compared with two significant differences (P <0.05); Single bladder cancer and multiple bladder cancer MVD respectively (38.4±10.6) (32.1±8.2) there was no significant difference between the two; early recurrence of bladder cancer and bladder cancer MVD respectively (30.1±5.7) (41.8±10.6) both more significant difference (P <0.05); aged≥60 years of age and age <60 years old, respectively MVD (35.5±3.6) (34.6±6.0), there was no significant difference between the two.3 ET-1 expression in positive MVD (38.6±5.9), ET-1 expression negative MVD (30.5±4.8), there are significant correlation (t=2.637, P <0.01).Conclusion:1 Bladder transitional cell carcinoma of ET-1 expression, the distribution of MVD was significantly higher than that in normal tissues.2 ET-1 and MVD in bladder transitional cell carcinoma of the grading and staging, initial and recurrent, have significant differences.3 ET-1 can promote the formation of tumor blood vessels.4 ET-1 expression and MVD can be used as the detection of bladder cancer degree of malignancy and invasiveness, as well as the criteria for determining the prognosis.