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使用定量图像分析,血管内皮生长因子C和D是结直肠癌新的预后标志物。

Vascular endothelial growth factors C and D represent novel prognostic markers in colorectal carcinoma using quantitative image analysis.

作者信息

Hu W-G, Li J-W, Feng B, Beveridge M, Yue F, Lu A-G, Ma J-J, Wang M-L, Guo Y, Jin X-L, Zheng M-H

机构信息

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.

出版信息

Eur Surg Res. 2007;39(4):229-38. doi: 10.1159/000101855. Epub 2007 Apr 19.

DOI:10.1159/000101855
PMID:17446709
Abstract

BACKGROUND/AIMS: Vascular endothelial growth factor C (VEGF-C) and vascular endothelial growth factor D (VEGF-D) are potent lymphangiogenic and angiogenetic mediators in many kinds of tumors. However, the exact impacts of VEGF-C and VEGF-D on the prognosis of colorectal cancer (CRC) remain elusive. The aims of this study were to demonstrate the expression of VEGF-C and VEGF-D and to correlate their expression levels with clinicopathological factors and long-term survival in patients with CRC.

PATIENTS AND METHODS

Between January 1996 and January 1998, 69 patients with pathologically confirmed CRC who received routine follow-up at the Ruijin Hospital were included in this study. VEGF-C and VEGF-D protein expression and microvessel density of 69 surgical specimens were assessed by immunohistochemistry, with 20 samples of normal colorectal tissues as controls. All patients were followed up for 108 months or until death. The Immunohistochemical stains were quantified and analyzed by means of a Zeiss Axioplan 2 imaging analysis system.

RESULTS

The protein expression of VEGF-C and VEGF-D in tumor tissues was much higher than that in normal colorectal tissues (p < 0.01). The VEGF-C expression significantly correlated with lymph node metastasis (p = 0.011) and clinical stages of CRC (p < 0.01). The VEGF-D expression correlated with patient ages (p = 0.013), depth of tumor invasion (p = 0.013), and lymph node metastasis (p = 0.028). The expression of VEGF-C and VEGF-D was significantly correlated with the microvessel density. Both overall survival and disease-free survival at 108 months were significantly lower in the CRC patients with a high VEGF-C and/or a high VEGF-D expression, and the patients with a high expression of both VEGF-C and VEGF-D had the shortest overall survival and disease-free survival when compared with other patients.

CONCLUSION

The VEGF-C or VEGF-D expression was significantly correlated with lymph node metastasis and long-term prognosis and could be applied as prognostic markers in CRC.

摘要

背景/目的:血管内皮生长因子C(VEGF-C)和血管内皮生长因子D(VEGF-D)是多种肿瘤中强大的淋巴管生成和血管生成介质。然而,VEGF-C和VEGF-D对结直肠癌(CRC)预后的确切影响仍不明确。本研究的目的是证实VEGF-C和VEGF-D的表达,并将其表达水平与CRC患者的临床病理因素及长期生存情况相关联。

患者与方法

1996年1月至1998年1月期间,69例在瑞金医院接受常规随访且经病理确诊为CRC的患者纳入本研究。采用免疫组织化学方法评估69例手术标本中VEGF-C和VEGF-D蛋白表达及微血管密度,以20例正常结直肠组织样本作为对照。所有患者随访108个月或直至死亡。通过蔡司Axioplan 2成像分析系统对免疫组织化学染色进行定量和分析。

结果

肿瘤组织中VEGF-C和VEGF-D的蛋白表达明显高于正常结直肠组织(p < 0.01)。VEGF-C表达与淋巴结转移(p = 0.011)及CRC临床分期(p < 0.01)显著相关。VEGF-D表达与患者年龄(p = 0.013)、肿瘤浸润深度(p = 0.013)及淋巴结转移(p = 0.028)相关。VEGF-C和VEGF-D的表达与微血管密度显著相关。VEGF-C和/或VEGF-D高表达的CRC患者108个月时的总生存率和无病生存率均显著降低,与其他患者相比,VEGF-C和VEGF-D均高表达的患者总生存期和无病生存期最短。

结论

VEGF-C或VEGF-D表达与淋巴结转移及长期预后显著相关,可作为CRC的预后标志物。

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