Ozer E, Mungan M U, Tuna B, Kazimoğlu H, Yörükoğlu K, Kirkali Z
Department of Pathology, Dokuz Eylül University School of Medicine, Inciralti, Izmir, Turkey.
Urology. 1999 Jul;54(1):50-5. doi: 10.1016/s0090-4295(99)00026-6.
To assess the prognostic significance of biologic parameters such as angiogenesis, expression of cathepsin D (a lysosomal protease), and degradation of type IV collagen (a basement membrane protein), we studied 20 patients with primary grade III Stage T1 transitional cell carcinoma of the bladder.
Endothelial cells were labeled immunohistochemically using factor VIII-related antigen. The vascular surface density (VSD) and the microvessel number (NVES) were assessed by means of stereology. The tumor tissues were also analyzed by immunohistochemical methods for the expression of cathepsin D and the staining pattern of type IV collagen.
Eight patients (40%) having either recurrence or progressive disease showed greater NVES and VSD values (P = 0.002 and P = 0.01, respectively) than patients without. The significance of vascular parameters was found to be statistically independent from coexisting carcinoma in situ, bacille Calmette-Guerin (BCG) treatment, tumor size, and number. Additionally, these parameters did not show statistical significance between progressive and recurrent tumors. However, tumors with solid morphologic features had higher VSD values and a significantly greater rate of recurrence or progression (P = 0.01 and P = 0.07, respectively). Tissue from 17 (85%) of 20 tumors showed absent or patchy basement membrane staining for type IV collagen, and 12 (60%) showed strong immunoreactivity for cathepsin D antibody. There were no differences for either molecule with either BCG treatment or other parameters related to prognosis.
Angiogenesis may have an independent role in predicting prognosis in grade III Stage T1 bladder carcinoma. Grade III Stage pT1 tumors with solid morphologic features have higher angiogenetic activity and a worse prognosis. Cathepsin D and type IV collagen do not seem to play a role in predicting biologic behavior.
为评估诸如血管生成、组织蛋白酶D（一种溶酶体蛋白酶）的表达以及IV型胶原（一种基底膜蛋白）降解等生物学参数的预后意义，我们研究了20例原发性膀胱移行细胞癌III级T1期患者。
采用免疫组织化学方法，使用VIII因子相关抗原标记内皮细胞。通过体视学评估血管表面密度（VSD）和微血管数量（NVES）。还采用免疫组织化学方法分析肿瘤组织中组织蛋白酶D的表达和IV型胶原的染色模式。
8例（40%）出现复发或疾病进展的患者的NVES和VSD值高于未出现复发或疾病进展的患者（分别为P = 0.002和P = 0.01）。发现血管参数的意义在统计学上独立于并存的原位癌、卡介苗（BCG）治疗、肿瘤大小和数量。此外，这些参数在进展性肿瘤和复发性肿瘤之间未显示统计学意义。然而，具有实性形态特征的肿瘤具有更高的VSD值以及显著更高的复发或进展率（分别为P = 0.01和P = 0.07）。20个肿瘤中有17个（85%）的组织显示IV型胶原的基底膜染色缺失或呈斑片状，12个（60%）显示对组织蛋白酶D抗体有强免疫反应性。对于这两种分子，在BCG治疗或其他与预后相关的参数方面均无差异。
血管生成可能在预测III级T1期膀胱癌的预后中具有独立作用。具有实性形态特征的III级pT1期肿瘤具有更高的血管生成活性和更差的预后。组织蛋白酶D和IV型胶原似乎在预测生物学行为方面不起作用。
