Expression of angiopoietins and its clinical significance in non-small cell lung cancer.
Expression of angiopoietins and its clinical significance in non-small cell lung cancer.
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发表时间：
2002-12
期刊：
影响因子：
11.2
通讯作者：
F. Tanaka;S. Ishikawa;K. Yanagihara;R. Miyahara;Y. Kawano;Mio Li;Y. Otake;H. Wada
中科院分区：
文献类型：
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作者：
F. Tanaka;S. Ishikawa;K. Yanagihara;R. Miyahara;Y. Kawano;Mio Li;Y. Otake;H. Wada
血管生成素（Angiopoietin，Ang）-1和-2是近年来发现的与血管内皮生长因子（vascular endothelial growth factor，VEGF）共同发挥作用的强有力的促血管生成因子，但关于Ang表达的临床研究尚未见报道。为了评估Ang在非小细胞肺癌（NSCLC）中表达的临床意义，对236例病理学I-IIIA期疾病患者进行了回顾性分析。免疫组化法检测肿瘤组织中Ang-1、Ang-2和VEGF的表达，免疫组化法检测肿瘤微血管密度（IMVD），免疫组化法检测肿瘤微血管密度（IMVD），免疫组化法检测肿瘤微血管密度（IMVD）中泛内皮细胞标记物CD 34（CD 34-IMVD）和增殖性内皮细胞标记物CD 105（CD 105-IMVD）。Ang-1阳性表达101例（42.8%），Ang-2阳性表达40例（16.9%）。Ang-1表达与CD 34-IMVD、CD 105-IMVD无明显相关性。相比之下，Ang-2阳性肿瘤的平均CD 105-IMVD显著高于Ang-2阴性肿瘤（56.7比38.5; P = 0.032）。更有趣的是，Ang-2的这种血管生成作用仅在VEGF高表达时可见;当VEGF高表达时，Ang-2阳性肿瘤的平均CD 105-IMVD显著高于Ang-2阴性肿瘤（89.1 vs 63.6; P = 0.045）;当VEGF表达较低时，Ang-2阳性肿瘤和Ang-2阴性肿瘤的平均CD 105-IMVD几乎相同（分别为27.4和27.1）。此外，Ang-2阳性表达，而不是Ang-1，是预测术后生存率差的重要因素（Ang-2阳性患者和阴性患者的5年生存率分别为53.5%和70.3%; P = 0.027），这一点得到了多变量分析的证实。当VEGF表达高时，Ang-2状态对术后生存的影响增强。也就是说，与Ang-2阴性和VEGF低的患者（66.6%）、与Ang-2阳性和VEGF低的患者（63.6%）以及与Ang-2阴性和VEGF低的患者（71.8%）相比，Ang-2阳性和VEGF高的患者的5年生存率极低（41.4%）。总之，Ang-2阳性表达与预后不良以及切除的非小细胞肺癌中的侵袭性血管生成显着相关，这种血管生成在VEGF高表达的情况下增强。
Angiopoietin (Ang)-1 and -2 have been recently identified as potent angiogenic factors which function in concert with vascular endothelial growth factor (VEGF), but no detailed clinical study on Ang expression has been reported. To assess the clinical significance of Ang expression in non-small cell lung cancer (NSCLC), a total of 236 patients with pathological stage-I-IIIA disease were retrospectively reviewed. Expression of Ang-1, Ang-2, or VEGF was examined immunohistochemically; intratumoral microvessel density (IMVD) was examined with immunohistochemical staining against CD34, a marker of pan-endothelial cells (CD34-IMVD), and that against CD105, a marker of proliferative endothelial cells (CD105-IMVD). Positive expression of Ang-1 and that of Ang-2 were seen in 101 (42.8%) and 40 patients (16.9%), respectively. There was no significant correlation between Ang-1 expression and CD34-IMVD or CD105-IMVD. In contrast, the average CD105-IMVD for Ang-2-positive tumor was significantly higher than that for Ang-2-negative tumor (56.7 versus 38.5; P = 0.032). More interestingly, such an angiogenic effect of Ang-2 was seen only when VEGF expression was high; when VEGF expression was high, the average CD105-IMVD for Ang-2-positive tumor was significantly higher than that for Ang-2-negative tumor (89.1 versus 63.6; P = 0.045); when VEGF expression was low, the average CD105-IMVD for Ang-2-positive tumor and that for Ang-2-negative tumor were almost the same (27.4 and 27.1, respectively). Moreover, positive expression of Ang-2, not Ang-1, was a significant factor to predict a poor postoperative survival (5-year survival rates for Ang-2-positive patients and -negative patients were 53.5 and 70.3%, respectively; P = 0.027), which was confirmed by a multivariate analysis. The influence of Ang-2 status on postoperative survival was enhanced when VEGF expression was high. That said, the 5-year survival of Ang-2-positive and VEGF-high patients was extremely low (41.4%) as compared with that for Ang-2-negative and VEGF-low patients (66.6%), as compared with that for Ang-2-positive and VEGF-low patients (63.6%), and as compared with that for Ang-2-negative and VEGF-low patients (71.8%). In conclusion, positive Ang-2 expression was significantly correlated with a poor prognosis, as well as with aggressive angiogenesis in resected NSCLC that was enhanced in the presence of high VEGF expression.