Bochner B H, Cote R J, Weidner N, Groshen S, Chen S C, Skinner D G, Nichols P W
Department of Urology, University of Southern California School of Medicine, Kenneth Norris Jr. Comprehensive Cancer Center, Los Angeles 90033, USA.
J Natl Cancer Inst. 1995 Nov 1;87(21):1603-12. doi: 10.1093/jnci/87.21.1603.
Tumor stage, histologic grade, and regional lymph node status are currently used to obtain prognostic information about bladder cancers. However, additional prognostic indicators are needed to aid clinicians in selecting patients who would benefit most from specific therapies. A majority of studies assessing the prognostic value of measuring tumor angiogenesis (i.e., measurement of tumor microvessel densities) have found a positive association between increasing microvessel densities and worsening prognosis.
We explored the relationship between established prognostic indicators and the extent of tumor-associated angiogenesis in patients with invasive transitional cell carcinoma (TCC) of the bladder, and we determined whether tumor microvessel density measurement could be used independently to predict bladder tumor behavior.
Tumor tissue was obtained from 164 patients with invasive primary TCC of the bladder. The extent of tumor-associated angiogenesis in this tissue was evaluated by immunohistochemical methods using HPCA-1, a mouse monoclonal antibody directed against the endothelial cell antigen, CD34. The number of microvessels in a 200x microscopic high-power field (hpf) containing the area of greatest neovascularization within or immediately adjacent to each tumor was determined. The patient population was then divided into three equivalently sized groups, with tumors containing low (< or = 64), intermediate (65-99), or high (> or = 100) numbers of microvessels per hpf. Kaplan-Meier product limit estimates of overall survival and the complement of cumulative incidence curves for recurrence-free survival were plotted. When analyzing survival or recurrence, the logrank test was used to compare groups of patients with and without stratification according to tumor stage. Analysis of variance was used to test for an association between microvessel density and established prognostic variables. Reported P values are from two-sided tests.
Microvessel density was significantly associated with disease-free (P < .0001) and overall (P = .0007) survival. The estimated probabilities of recurrence at 5 years were 19% (95% confidence interval [CI] = 8-29), 56% (95% CI = 43-69), and 68% (95% CI = 55-81) for patients with lowest, intermediate, and highest microvessel counts, respectively. Overall survival at 5 years was estimated to be 68% (95% CI = 56-81), 44% (95% CI = 30-57), and 34% (95% CI = 21-47) for the same three patient groups. Microvessel density was associated with disease progression in patients with organ-confined tumors, tumors extending through the bladder wall, and tumors that had spread to regional lymph nodes. Tumor angiogenesis was found to be an independent prognostic indicator when evaluated in the presence of histologic grade, pathologic stage, and regional lymph node status.
Tumor angiogenesis, as determined by microvessel density measurement, is an independent prognostic indicator for patients with invasive TCC of the bladder.
肿瘤分期、组织学分级和区域淋巴结状态目前用于获取膀胱癌的预后信息。然而，需要额外的预后指标来帮助临床医生选择能从特定治疗中获益最大的患者。大多数评估肿瘤血管生成测量（即肿瘤微血管密度测量）预后价值的研究发现，微血管密度增加与预后恶化之间存在正相关。
我们探讨了既定预后指标与膀胱浸润性移行细胞癌（TCC）患者肿瘤相关血管生成程度之间的关系，并确定肿瘤微血管密度测量是否可独立用于预测膀胱肿瘤行为。
从164例膀胱原发性浸润性TCC患者中获取肿瘤组织。使用针对内皮细胞抗原CD34的小鼠单克隆抗体HPCA-1，通过免疫组化方法评估该组织中肿瘤相关血管生成的程度。确定每个肿瘤内部或紧邻肿瘤的新生血管最丰富区域的200倍显微镜高倍视野（hpf）中的微血管数量。然后将患者群体分为三个大小相等的组，每组肿瘤每hpf的微血管数量低（≤64）、中等（65 - 99）或高（≥100）。绘制总体生存的Kaplan-Meier乘积限估计值和无复发生存累积发病率曲线的互补曲线。在分析生存或复发情况时，使用对数秩检验比较根据肿瘤分期分层和未分层的患者组。方差分析用于检验微血管密度与既定预后变量之间的关联。报告的P值来自双侧检验。
微血管密度与无病生存（P <.0001）和总体生存（P =.0007）显著相关。微血管计数最低、中等和最高的患者5年复发估计概率分别为19%（95%置信区间[CI] = 8 - 29）、56%（95% CI = 43 - 69）和68%（95% CI = 55 - 81）。相同的三组患者5年总体生存估计分别为68%（95% CI = 56 - 81）、44%（95% CI = 30 - 57）和34%（95% CI = 21 - 47）。微血管密度与器官局限性肿瘤、穿透膀胱壁的肿瘤以及已扩散至区域淋巴结的肿瘤患者的疾病进展相关。在存在组织学分级、病理分期和区域淋巴结状态的情况下进行评估时，发现肿瘤血管生成是一个独立的预后指标。
通过微血管密度测量确定的肿瘤血管生成是膀胱浸润性TCC患者的独立预后指标。
