Charpin-Taranger Colette, Dales Jean-Philippe, Garcia Stephane, Andrac-Meyer Lucile, Ramuz Olivier, Carpentier-Meunier S, Bonnier Pascal
Faculté de Médecine Secteur Nord, service d'Anatomie et Cytologie Pathologiques, Boulevard Pierre Dramard-Marseille, France.
Bull Acad Natl Med. 2003;187(6):1129-45; discussion 1145-6.
The quantification of angiogenesis in human solid tumors has been shown to be an indicator of prognosis and tumor microvasculature is a candidate target for antiangiogenic therapy. CD105 (endoglin) is significantly expressed in activated endothelial cells in culture and in tumor microvessels. Quantification of CD105 immunocytochemical expression that may be of significant clinical relevance, has not been accurately evaluated as yet. In the present report, CD105 expression on frozen sections was investigated using immunohistochemical assays in a series of 929 patients and correlated with long-term (median = 11.3 years) follow-up. The CD105 immunostaining was observed on endothelial cells mostly in small cells. The number of vessels and the immunostained surface were evaluated in so called "hot spots" within tumor stroma. Both the number of vessels and immunostained surface were correlated to the patients' outcome (overall survival, disease free survival, metastases) in the whole group of patients and also specifically in node negative subgroup. Univariate (Kaplan Meier) analysis showed that the number of CD105 positive microvessels (cut-off n = 15) was significantly correlated with poor overall survival, among all patients (p = 0.001). This correlation was less significant in the group of node negative patients (p = 0.035). Marked CD105 expression was also correlated with high metastasis risk among all patients (p = 0.006) and among node negative patients as well (p = 0.001). In multivariate analysis (Cox model) CD105 immunodetection was identified as an independent prognostic indicator. Our results suggest that CD105 immunohistochemical expression has a practical clinical relevance for identifying node negative patients with poor prognosis. Moreover, the CD105 immunodetection may also be considered as a potential tool for selecting patients that could benefit from specific antiangiogenic therapy, using anti CD105 conjugates.
人体实体瘤血管生成的定量分析已被证明是一种预后指标,肿瘤微血管是抗血管生成治疗的候选靶点。CD105(内皮糖蛋白)在培养的活化内皮细胞和肿瘤微血管中显著表达。CD105免疫细胞化学表达的定量分析可能具有重要的临床意义,但尚未得到准确评估。在本报告中,我们采用免疫组织化学方法对929例患者的冰冻切片进行了CD105表达研究,并与长期(中位数=11.3年)随访结果相关联。CD105免疫染色主要在内皮细胞的小细胞中观察到。在肿瘤基质内的所谓“热点”区域评估血管数量和免疫染色面积。血管数量和免疫染色面积与整个患者组以及淋巴结阴性亚组患者的预后(总生存期、无病生存期、转移情况)均相关。单因素(Kaplan Meier)分析显示,在所有患者中,CD105阳性微血管数量(截断值n = 15)与较差的总生存期显著相关(p = 0.001)。在淋巴结阴性患者组中,这种相关性较弱(p = 0.035)。显著的CD105表达在所有患者中(p = 0.006)以及淋巴结阴性患者中(p = 0.001)也与高转移风险相关。在多因素分析(Cox模型)中,CD105免疫检测被确定为独立的预后指标。我们的结果表明,CD105免疫组织化学表达对于识别预后不良的淋巴结阴性患者具有实际临床意义。此外,CD105免疫检测也可被视为一种潜在工具,用于选择可能从使用抗CD105偶联物的特定抗血管生成治疗中获益的患者。