Oda Yoshinao, Yamamoto Hidetaka, Tamiya Sadafumi, Matsuda Shuichi, Tanaka Kazuhiro, Yokoyama Ryohei, Iwamoto Yukihide, Tsuneyoshi Masazumi
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka, Japan.
Mod Pathol. 2006 May;19(5):738-45. doi: 10.1038/modpathol.3800587.
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 +/- 6.87/0.26 mm2 vs metastatic, 43.32 +/- 8.65/0.26 mm2; 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 +/- 5.4 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.
趋化因子CXCL12及其受体CXCR4最近被证明在几种癌症的转移中起重要作用。也有研究表明，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例骨肉瘤患者原发部位和相应肺转移部位CXCR4和VEGF的免疫组化表达情况，所有患者均接受了开胸手术。还评估了CD34免疫染色显示的微血管密度（MVD）以及MIB-1单克隆抗体检测的增殖活性。转移部位的CXCR4表达（原发部位，阳性率33.3%；转移部位，阳性率66.6%；P = 0.0097）和MVD（原发部位，29.86±6.87/0.26 mm2；转移部位，43.32±8.65/0.26 mm2；P = 0.0015）均显著高于原发部位，而原发部位和转移部位在VEGF表达方面未观察到差异。免疫组化CXCR4和VEGF表达之间存在显著正相关（P = 0.0269）。在总体人群中，VEGF免疫反应阳性的肿瘤MIB-1标记指数（LI）显著更高（VEGF阳性肿瘤的MIB-1-LI为24.29±5.4，VEGF阴性肿瘤为18.33±4.16；P = 0.034）。此外，VEGF阳性原发肿瘤患者的预后明显比VEGF阴性原发肿瘤患者差（P = 0.0053）。我们的结果表明，CXCR4表达与转移进展相关，原发部位的免疫组化VEGF表达对发生肺转移的骨肉瘤患者具有预测价值。
