CXCR4 and VEGF expression in the primary site and the metastatic site of human osteosarcoma: analysis within a group of patients, all of whom developed lung metastasis
CXCR4 and VEGF expression in the primary site and the metastatic site of human osteosarcoma: analysis within a group of patients, all of whom developed lung metastasis
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DOI：
10.1038/modpathol.3800587
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发表时间：
2006-05-01
期刊：
影响因子：
7.5
通讯作者：
Tsuneyoshi, M
中科院分区：
文献类型：
--
作者：
Oda, Y;Yamamoto, H;Tsuneyoshi, M
趋化因子CXCL12及其受体CXCR4最近被证明在多种癌症的转移中发挥重要作用。研究还表明，VEGF 可调节乳腺癌细胞系中 CXCR4 的表达和侵袭性。我们比较了 30 名骨肉瘤患者的原发部位和一致肺转移部位之间 CXCR4 和 VEGF 的免疫组织化学表达，所有这些患者都接受了开胸手术。还评估了 CD34 免疫染色显示的微血管密度 (MVD) 和 MIB-1 单克隆抗体的增殖活性。与对照组相比，转移部位的 CXCR4 表达（原发性，33.3% 阳性 vs 转移性，66.6% 阳性；P = 0.0097）和 MVD（原发性，29.86 +/- 76.87/0.26 mm(2) vs 转移性，43.32 +/- 78.65/ 0.26mm(2)；P = 0.0015）均显着增加那些在主站点中，而没有 观察到原发部位和转移部位之间 VEGF 表达的差异。免疫组化CXCR4与VEGF表达呈显着正相关（P=0.0269）。在总人群中，肿瘤中的 MIB-1 标记指数 (LI) 显着较高，显示出 VEGF 的免疫反应性（VEGF 阳性肿瘤中的 MIB-1-LI 为 24.29 +/- 75.4，而 VEGF 阴性肿瘤中为 18.33 +/- 4.16；P = 0.034）。此外，与VEGF阴性原发肿瘤患者相比，VEGF阳性原发肿瘤患者的预后显着较差（P=0.0053）。我们的结果表明，CXCR4 表达与转移进展相关，原发部位的免疫组织化学 VEGF 表达对发生肺转移的骨肉瘤患者具有预测价值。
The chemokine, CXCL12, and its receptor, CXCR4, have recently been shown to play an important role in metastasis of several kinds of carcinoma. It has also been demonstrated that VEGF regulates both the expression of CXCR4 and invasiveness in breast cancer cell lines. We compared the immunohistochemical expression of CXCR4 and VEGF between the primary site and a concordant pulmonary metastatic site in 30 osteosarcoma patients, all of which had undergone thoracotomy. Microvessel density (MVD) as shown by immunostaining of CD34 and proliferative activity with MIB-1 monoclonal antibody was also evaluated. CXCR4 expression ( primary, 33.3% positive vs metastatic, 66.6% positive; P = 0.0097) and MVD ( primary, 29.86 +/- 76.87/0.26 mm(2) vs metastatic, 43.32 +/- 78.65/ 0.26mm(2); P = 0.0015) in the metastatic site were both significantly increased compared with those in the primary site, whereas no difference between primary and metastatic sites was observed with regard to VEGF expression. There was a significant positive correlation between immunohistochemical CXCR4 and VEGF expression ( P = 0.0269). In total population, the MIB-1-labeling index (LI) was significantly higher in tumors, which showed immunoreactivity for VEGF (MIB-1-LI in VEGF-positive tumors, 24.29 +/- 75.4 vs VEGF-negative tumors, 18.33 +/- 4.16; P = 0.034). Furthermore, those patients with VEGF-positive primary tumors had a significantly worse prognosis compared with the patients with VEGF-negative primary tumors ( P = 0.0053). Our results suggested that CXCR4 expression was associated with metastatic progression, and immunohistochemical VEGF expression in the primary site had predictive value for the osteosarcoma patients, who developed lung metastasis.