الفهرس 
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Abstract
This study aimed at assessment of angiogenesis and vascular invasion, in both bilharzia- and non-bilharzia-associated, human urothelial bladder cancer and their correlation with the pathological features of such tumors.
The tumors from 40 males and 10 females (mean age 61.6 ± 9.9 years) were examined. Vessels were stained using an antibody to the platelet endothelial cell adhesion molecule, CD31. Microvessels were counted in active areas of angiogenesis within the tumors. Microvessel density (MVD) was quantified using the mean of three counts. CD31 immunostaining was also used to detect vascular invasion by tumor. Tumor cells were stained using VEGF monoclonal antibody, an important promoter of angiogenesis, and immunoreactivity was evaluated according to two scoring systems; staining intensity and percentage of stained cells, then combining these two scores. MVD and VEGF scores as well as vascular invasion were evaluated in relation to tumor grade, stage, muscle invasion, presence of divergent histologic differentiation, bilharzia association and lymph node metastasis.
The MVD ranged from 0 to 201, and by using the ROC curve, the cut off point of MVD in relation to muscle invasion was 20. MVD-20 had high significant relation (p=0.000) with each of tumor stage, muscle invasion, grade and presence of divergent differentiation. However, there was no significant relation with associated bilharziasis.
Eight cases (16%) showed vascular invasion assessed by CD31 staining of endothelial cells and the presence of vascular invasion was significantly correlated with tumor stage (p=0.02), muscle invasion (p=0.04) and MVD-20 (p=0.04), however, it was not significantly related to tumor grade, divergent differentiation, lymph node metastases or associated bilharziasis.
78% of cases showed high VEGF expression, and VEGF score was significantly related (p=0.005) to lymph node metastases, but was not related to the other parameters or bilharzia association.
It is apparent from the results of the present study that angiogenesis in urothelial carcinoma plays an important role in determining the tumor’s behavior particularly its propensity to local and distant spread and consequently its prognosis. Hence assessment of angiogenesis may provide useful insight into developing new treatment modalities based on blocking the neovascularization process and thereby limiting tumor progression.
The effect of associated bilharziasis on angiogenesis in urothelial tumors was not evident in this study. Further studies with more sample size are thus recommended to clarify this relation, and also to compare the effect of bilharzial association between squamous and transitional tumors.
The assessment of angiogenesis and vascular invasion appears to have important clinical implications in both TURT and radical cystectomy specimens:
In TURT specimens, the presence of vascular invasion is a sure sign of invasiveness of the tumor and suggests higher tumor stage after radical cystectomy, so neoadjuvant chemotherapy is indicated prior to cystectomy in those cases. Also, in TURT specimens, if MVD is more than 20, this indicates muscle invasion, and suggests high stage, high grade and presence of divergent differentiation.
In radical cystectomy specimens, a high VEGF expression suggests the presence of positive lymph node metastases. This is particularly important in cases with negative node metastases, either radiologically or in routine pathological sections, as nodal micro metastases might be overlooked. These patients are recommended to receive adjuvant chemotherapy after cystectomy. Moreover, the significant correlation of MVD and vascular invasion suggests that tumors having MVD more than 20 are more liable to have vascular invasion and distant metastases, even if vascular invasion is not detected in tumor sections and thus MVD can stratify patients who may need aggressive treatment following cystectomy.