Bartoletti Riccardo, Cai Tommaso, Nesi Gabriella, Sardi Iacopo, Rizzo Michelangelo
Department of Urology, University of Florence, Viale Pieraccini 18, 50139 Florence, Italy.
Oncol Rep. 2005 Jul;14(1):251-5.
Many authors have shown that tumor hypoxia exerts its own influence on malignant progression by inducing angiogenetic factors and new blood vessels inside and around the tumor. This event usually suggests a poor prognosis and/or aggressive tumor behavior. The objective of the present study is to compare molecular analysis of angiogenetic factors with microvessel density (MVD) in bladder carcinoma. Twenty-nine consecutive patients underwent transurethral or open surgery for bladder tumors. Neoplastic tissue samples, normal-appearing bladder mucosa and blood samples were taken from each patient. All the tissues underwent mRNA extraction and Northern blot analysis, marked with specific probes for inducible nitric oxide sinthase (iNOS), cyclo-oxygenase-2 (cox-2), vascular endothelial growth factor (VEGF) and were evaluated by gel-electrophoresis. Microvessel density, a quantitative analysis for neoangiogenesis, was also evaluated by using CD31 immunohistochemical assay and compared with both molecular analysis and patient follow-up. Two follow-up for recurrence and/or progression were performed at 74 months and 10 years from surgery respectively. Pathological evaluation demonstrated the presence of superficial transitional cell carcinoma (sTCC) in 15 patients, while 14 had an invasive bladder tumor (iBT). At both 74 months and 10 years follow-up, all patients with lower MVD had a shorter survival time. No significant results were obtained by comparing disease progression or survival rate with VEGF, iNOS and COX-2 levels. A proportional increase of VEGF expression and MVD compared with poor prognosis was the expected outcome of our study. These results were disregarded at both the 1st and the 2nd follow-up. A strong association between MVD>20 and survival rate was noted both in sTCC (p=0.024) and iBT (p>0.001) patients. These results confirm that MVD could be considered a good prognostic factor. The angiogenetic cytokines overexpression found in control tissue samples of sTCC could have clinical significance, either as a macroscopically unidentified diffuse carcinogenetic process or the presence of a systemic immune-response against tumor cells.
许多作者已经表明，肿瘤缺氧通过诱导肿瘤内部和周围的血管生成因子及新血管，对恶性进展产生自身影响。这一情况通常提示预后不良和/或肿瘤行为侵袭性强。本研究的目的是比较膀胱癌中血管生成因子的分子分析与微血管密度（MVD）。29例连续的患者因膀胱肿瘤接受了经尿道或开放手术。从每位患者身上采集肿瘤组织样本、外观正常的膀胱黏膜和血液样本。所有组织均进行mRNA提取和Northern印迹分析，用诱导型一氧化氮合酶（iNOS）、环氧化酶-2（cox-2）、血管内皮生长因子（VEGF）的特异性探针进行标记，并通过凝胶电泳进行评估。微血管密度是对新生血管形成的定量分析，也通过使用CD31免疫组织化学检测进行评估，并与分子分析和患者随访结果进行比较。分别在术后74个月和10年进行了两次复发和/或进展随访。病理评估显示，15例患者存在浅表性移行细胞癌（sTCC），而14例患有浸润性膀胱肿瘤（iBT）。在74个月和10年的随访中，所有MVD较低的患者生存时间均较短。将疾病进展或生存率与VEGF、iNOS和COX-2水平进行比较，未获得显著结果。与预后不良相比，VEGF表达和MVD成比例增加是我们研究的预期结果。在第一次和第二次随访中，这些结果均未得到重视。在sTCC（p = 0.024）和iBT（p>0.001）患者中，均发现MVD>20与生存率之间存在强关联。这些结果证实MVD可被视为一个良好的预后因素。在sTCC的对照组织样本中发现的血管生成细胞因子过表达可能具有临床意义，要么是作为一种宏观上未被识别的弥漫性致癌过程，要么是存在针对肿瘤细胞的全身免疫反应。
