Angiopoietins lack of prognostic significance in ductal mammary carcinoma.
Angiopoietins lack of prognostic significance in ductal mammary carcinoma.
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血管生成素对乳腺导管癌缺乏预后意义。
DOI：
10.1186/1477-7800-4-6
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发表时间：
2007-03-23
期刊：
影响因子：
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通讯作者：
Jiang, Wen G
中科院分区：
文献类型：
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作者：
Rmali, Khaled A;Watkins, Gareth;Douglas-Jones, Antonio;Mansel, Robert E;Jiang, Wen G
血管生成素（Angiopoietins，Ang）在肿瘤血管生成过程中起重要作用。不同的血管生成素在血管生成过程中具有不同的作用。本研究旨在检测Ang-1、Ang-2、Ang-3及其受体Tie-2在乳腺导管癌中的表达水平，并评估其与预后的相关性。使用新鲜冷冻的导管癌组织（n = 90）和邻近的非癌乳腺组织（n = 32）。采用定量RT-PCR方法检测Ang-1、Ang-2和Ang-3在乳腺癌组织和正常乳腺组织中的表达。采用免疫组化法检测Ang-1、Ang-2和Tie-2蛋白的表达。Ang-1、Ang-2、Ang-3在乳腺组织中均有表达。Ang-1在正常上皮细胞、乳腺癌细胞以及内皮细胞中均可见。Ang-2表达水平高于Ang-1，在上皮细胞、内皮细胞和间质细胞均有不同程度的表达。Ang-1和Ang-2在乳腺癌组织和正常乳腺组织中的表达量基本相同，而Ang-3在乳腺癌组织中的表达量高于正常乳腺组织，但差异无统计学意义（155 ± 123和24.1 ± 22.6，P > 0.05）。在具有不同预测预后的患者之间没有观察到显著差异（使用诺丁汉预后指数作为指导）（分别为Ang-1 p = 0.34、Ang-2 p = 0.26和Ang-3 p = 0.32）。Ang-1、Ang-2和Ang-3与肿瘤分级无明显相关性。当将转录物的水平与临床结果（无疾病、发生复发和死于乳腺癌的患者）进行比较时，发现具有骨转移的乳腺癌患者中Ang-3转录物的水平高33.8 ± 28.3，尽管差异不显著（p = 0.08）。Ang-1和Ang-2转录水平和临床结局无显著差异。此外，在队列中未观察到Tie-2受体与临床/病理学参数之间的显著趋势。这些数据表明，血管生成素（Ang-1，Ang-2和Ang-3）在乳腺组织中表达，在正常和肿瘤。这些分子在预测乳腺导管癌患者的预后和临床结局方面的价值有限。
Angiopoietins (Ang) have been shown to regulate the process of vasculature and angiogenesis in tumour. Different angiopoietins have different roles during the angiogenic process. The current study sought to examine the levels of the expression of Ang-1, Ang-2, Ang-3 and their receptor Tie-2 in mammary ductal carcinoma and to assess their relevance to prognosis. Fresh frozen ductal carcinoma tissues (n = 90) and adjacent non-cancerous breast tissues (n = 32) were used. The expression of Ang-1, Ang-2 and Ang-3 transcripts in cancer and normal breast tissues were examined quantitatively using quantitative RT-PCR. The protein expression of Ang-1, Ang-2 and Tie-2 was assessed by immunohistochemistry on frozen sectioned tissues. Ang-1, Ang-2 and Ang-3 were detected in mammary tissues. Ang-1 was seen in both normal epithelial cells, breast cancer cells as well as in endothelial cells. Ang-2 was seen at a higher level than Ang-1 and it is expressed in epithelial, endothelial as well as stromal cells to certain degree. Ang-1 and Ang-2 transcripts were detected almost equally in cancer and normal breast tissue, and Ang-3 was high in cancer tissue compared to normal breast but not significant (155 ± 123 & 24.1 ± 22.6, P > 0.05). No significant differences were seen between patients with different predicted prognosis (using the Nottingham Prognostic Index as a guide) (Ang-1 p = 0.34, Ang-2 p = 0.26 and Ang-3 p = 0.32, respectively). No significant correlation was seen between Ang-1, Ang-2 and Ang-3 with tumour grade. When the levels of the transcripts were compared against clinical outcome (disease free, developed recurrence and patients who died of breast cancer), levels of Ang-3 transcript was found to be high in breast cancer patient who had bone metastasis 33.8 ± 28.3, although the difference was not significant (p = 0.08). No significant difference was seen with levels of Ang-1 and Ang-2 transcripts and clinical outcomes. Furthermore, no significant trend was observed between Tie-2 receptor and clinical/pathological parameters in the cohort. These data suggest that angiopoietins (Ang-1, Ang-2 and Ang-3) are expressed in mammary tissues, both in normal and tumour. These molecules have limited value in predicting the prognosis and clinical outcome in patients with mammary ductal carcinoma.