Romani Antonello A, Borghetti Angelo F, Del Rio Paolo, Sianesi Mario, Soliani Paolo
Dipartimento di Medicina Sperimentale, Sezione di Patologia Molecolare ed Immunologia, Università degli Studi di Parma, Italy.
J Surg Oncol. 2006 May 1;93(6):446-55. doi: 10.1002/jso.20456.
Angiogenesis is a complex multistep process that involves extracellular matrix remodeling, migration and proliferation of endothelial cells, and morphogenesis of microvessels. CD105 (endoglin), a co-receptor of the TGF-beta superfamily, was proposed as a marker of neovascularization in solid malignancies. The aim of this study was to evaluate retrospectively the effect of CD105-assessed angiogenesis on the risk of developing metastatic disease in colorectal cancer (CRC).
One hundred and twenty-five paraffin-embedded samples were analyzed by immunohistochemical methods using a CD105 monoclonal antibody. The median follow-up was 70.8 months. Survivals were calculated from actuarial estimates, and logistic regression predicted the risk of developing metastatic disease.
The CD105-vessel count was strongly correlated with the occurrence of metastatic disease. The median CD105-positive vessels in patients with and without metastatic disease were 24.7 and 13.2 vessels/mm(2), respectively (P < 0.001). For each one microvessel increase in the vessels count per 400x field, there was a 1.42-fold increase in the risk of metastatic disease (P < 0.001).
The assessment of tumor angiogenesis with anti-CD105 was not sufficient for its use as a surrogate end point for survival because of the amount of survival variability explained was only 8% in absence of metastatic disease. In contrast, multivariate logistic regression analysis revealed that CD105-vessels count can identify patients at high risk of metastatic disease.
血管生成是一个复杂的多步骤过程，涉及细胞外基质重塑、内皮细胞迁移与增殖以及微血管形态发生。CD105（内皮糖蛋白）是转化生长因子-β超家族的一个共受体，被认为是实体恶性肿瘤新生血管形成的标志物。本研究的目的是回顾性评估通过CD105评估的血管生成对结直肠癌（CRC）发生转移疾病风险的影响。
使用CD105单克隆抗体通过免疫组织化学方法分析125个石蜡包埋样本。中位随访时间为70.8个月。通过精算估计计算生存率，逻辑回归预测发生转移疾病的风险。
CD105血管计数与转移疾病的发生密切相关。有和没有转移疾病的患者中，CD105阳性血管的中位数分别为24.7和13.2条/平方毫米（P < 0.001）。每400倍视野下血管计数每增加一个微血管，转移疾病的风险增加1.42倍（P < 0.001）。
由于在无转移疾病时生存变异性的解释量仅为8%，因此用抗CD105评估肿瘤血管生成不足以将其用作生存的替代终点。相比之下，多变量逻辑回归分析显示，CD105血管计数可以识别出转移疾病高风险患者。
