Funaki Hiroshi, Nishimura Genichi, Harada Shin-Ichi, Ninomiya Itasu, Terada Itsuro, Fushida Sachio, Tani Takashi, Fujimura Takashi, Kayahara Masato, Shimizu Koichi, Ohta Tetsuo, Miwa Koichi
Gastroenterologic Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan.
Oncology. 2003;64(4):416-22. doi: 10.1159/000070301.
Expression of vascular endothelial growth factor (VEGF)-D by tumors is associated with metastasis to lymph nodes in mice. However, there are few reports concerning the clinical significance of VEGF-D protein in human carcinoma.
After confirming production of VEGF-D by eight colorectal carcinoma cell lines, we investigated relationships between the expression of VEGF-D protein, lymph node metastasis and postoperative survival in 83 colorectal carcinoma patients. mRNA levels in cell lines were evaluated using the real-time reverse transcriptase-polymerase chain reaction, and protein was detected by Western blotting in cell lines and by immunohistochemistry in resected tissues using an antibody recognizing the processed form of the molecule.
Immunohistochemistry showed VEGF-D-positive staining in 26 of the 83 carcinomas (31%). There was a significant relationship between the presence of VEGF-D protein and the incidence of lymph node metastasis (p < 0.01). Multivariate logistic regression analysis revealed that VEGF-D protein expression was an independent factor affecting lymph node metastasis (p < 0.01). Nonetheless, the presence or absence of VEGF-D protein had no significant impact on the survival of the patients (p = 0.15).
These results suggest that the expression of VEGF-D protein could be useful in predicting the nodal status of colorectal carcinoma patients.
肿瘤中血管内皮生长因子(VEGF)-D的表达与小鼠淋巴结转移相关。然而,关于VEGF-D蛋白在人类癌症中的临床意义的报道较少。
在确认8种结肠癌细胞系产生VEGF-D后,我们研究了83例结肠癌患者中VEGF-D蛋白表达、淋巴结转移与术后生存之间的关系。使用实时逆转录聚合酶链反应评估细胞系中的mRNA水平,并通过蛋白质印迹法检测细胞系中的蛋白质,以及使用识别该分子加工形式的抗体通过免疫组织化学法检测切除组织中的蛋白质。
免疫组织化学显示83例癌组织中有26例(31%)VEGF-D呈阳性染色。VEGF-D蛋白的存在与淋巴结转移发生率之间存在显著关系(p<0.01)。多因素逻辑回归分析显示,VEGF-D蛋白表达是影响淋巴结转移的独立因素(p<0.01)。然而,VEGF-D蛋白的有无对患者的生存没有显著影响(p = 0.15)。
这些结果表明,VEGF-D蛋白的表达可能有助于预测结肠癌患者的淋巴结状态。