Kumar S, Ghellal A, Li C, Byrne G, Haboubi N, Wang J M, Bundred N
Department of Pathological Sciences, The University of Manchester, United Kingdom.
Cancer Res. 1999 Feb 15;59(4):856-61.
Angiogenesis is essential for tumor growth and metastasis. There are conflicting reports as to whether microvessel density (IMD) in breast cancers is associated with prognosis. This could be due to the use of different antibodies to endothelial cell markers, variation in tissue pretreatment protocols, and nonstandardized counting methods. We have assessed the IMD in 106 breast carcinomas using a pan-endothelial marker, CD34, and a recently described mAb to CD105, which preferentially reacts with endothelial cell in angiogenic tissues. IMD values (separated as above or below median) for CD105 expression showed a statistically significant correlation with overall (P = 0.0029) and disease-free survival (P = 0.0362). In contrast, blood vessel counts using a panendothelial marker CD34 did not correlate with overall or disease-free survival (P = 0.2912 and P = 03153, respectively). When IMD values were subdivided into quartiles and assessed for their prognostic values, there was a statistically significant difference in the overall survival across CD105, but not CD34, values (P = 0.0017 and P = 0.7997, respectively) and also disease-free survival (P = 0.0431 and P = 0.5066, respectively). Further analysis of IMD values demonstrated that there were no deaths in the lowest quartile for CD105 and it differed from the other three quartiles. However, examination of clinical details of patients in the lowest quartile failed to reveal clustering of patients known to be associated with low-risk factors. Multivariate analysis confirmed that IMD values using CD105 were an independent prognostic factor. These results suggest that the ability to quantitatively distinguish between tumor neovascularization and preexisting vessels may be important in the assessment of tumor angiogenesis, but requires confirmation in a greater number of patients with a longer follow-up.
血管生成对于肿瘤的生长和转移至关重要。关于乳腺癌中的微血管密度(MVD)是否与预后相关,存在相互矛盾的报道。这可能是由于使用了不同的内皮细胞标志物抗体、组织预处理方案的差异以及未标准化的计数方法。我们使用一种泛内皮标志物CD34和一种最近描述的针对CD105的单克隆抗体评估了106例乳腺癌中的MVD,该抗体优先与血管生成组织中的内皮细胞反应。CD105表达的MVD值(分为中位数以上或以下)与总生存期(P = 0.0029)和无病生存期(P = 0.0362)显示出统计学上的显著相关性。相比之下,使用泛内皮标志物CD34进行的血管计数与总生存期或无病生存期均无相关性(分别为P = 0.2912和P = 0.3153)。当将MVD值细分为四分位数并评估其预后价值时,CD105值与总生存期(分别为P = 0.0017和P = 0.7997)以及无病生存期(分别为P = 0.0431和P = 0.5066)之间存在统计学上的显著差异。对MVD值的进一步分析表明,CD105最低四分位数中没有死亡病例,且与其他三个四分位数不同。然而,对最低四分位数患者的临床细节检查未能发现已知与低风险因素相关的患者聚集情况。多变量分析证实,使用CD105的MVD值是一个独立的预后因素。这些结果表明,在评估肿瘤血管生成时,定量区分肿瘤新生血管和既有血管的能力可能很重要,但需要在更多患者中进行更长时间的随访以进行确认。