国际肿瘤学杂志

国际肿瘤学杂志 ›› 2013, Vol. 40 ›› Issue (10): 793-796.

• 论著 • 上一篇    下一篇

HIF-1α和VEGF-C在乳腺癌淋巴管生成中的作用机制

赵迎春, 李勇, 朱永云, 等   

  1. 241000 安徽省芜湖市第二人民医院乳腺外科（赵迎春、朱永云、罗传瑜），病理科（李勇）
  • 出版日期:2013-10-08 发布日期:2013-09-23
  • 通讯作者: 赵迎春，E-mail: lcy0508@hotmail.com E-mail:lcy0508@hotmail.com

Mechanisms of HIF-1αand VEGF-C on the lymphangiogenesis in breast carcinoma

ZHAO  Ying-Chun, LI  Yong, ZHU  Yong-Yun, et al   

  1. Department of Breast Surgery, Second People’s Hospital of Wuhu, Wuhu 241000, China
  • Online:2013-10-08 Published:2013-09-23
  • Contact: ZHAO Ying-chun E-mail:lcy0508@hotmail.com

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摘要： 目的  探讨缺氧诱导因子-1α(HIF-1α)、血管内皮生长因子C (VEGF-C)在乳腺癌中的表达及其与临床病理特征的关系，以及二者在乳腺癌淋巴管生成及淋巴结转移中的作用。方法  选择78例乳腺癌标本和20例乳腺良性病变标本，应用免疫组织化学染色方法，检测HIF-1α和VEGF-C的表达情况，采用D2-40标记淋巴管后进行淋巴管密度（LVD）计数，并对三者与临床病理参数的关系进行统计学分析。结果  乳腺癌中HIF-1α、VEGF-C的阳性表达率分别为66.67%（52/78）和52.56%（41/78），明显高于对照组的15%和10%（χ2=17.26，P=0.000；χ2=11.71，P=0.001）；乳腺癌组织中HIF-1α、VEGF-C的阳性表达与淋巴结转移(χ2=5.80，P=0.016；χ2=7.26，P=0.007)、临床分期(χ2=8.51，P=0.004；χ2=6.02，P=0.014)密切相关，但与患者的年龄、肿瘤直径、组织学分级、病理类型无明显相关性(P＞0.05)；HIF-1α与VEGF-C的阳性表达呈显著正相关(r=0.254，P=0.025)，乳腺癌组织中HIF-1α、VEGF-C阳性组LVD明显高于阴性组(t=2.19，P=0.017；t=3.25，P=0.001)。结论  HIF-1α可能通过调控VEGF-C的表达在乳腺癌淋巴管生成及淋巴结转移中起重要作用，其有望成为治疗乳腺癌淋巴结转移的新的作用靶点。

关键词: 缺氧诱导因子-1α, 血管内皮生长因子C, 淋巴管生成, 乳腺肿瘤

Abstract: Objective  To investigate the expressions of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor-C (VEGF-C) and the correlations with clinic parameters, and to make sure the effect of       DOI:10.3760/cma.j.issn.1673-422X.2013.10. 基金项目：安徽省卫生厅自然科学基金（09C230）作者单位：241000 安徽省芜湖市第二人民医院乳腺外科（赵迎春、朱永云、罗传瑜），病理科（李勇）通信作者：赵迎春，E-mail: lcy0508@hotmail.com 联系人: 赵迎春  lcy0508@hotmail.com   电话：05533909558 手机：18155317401 the two genes in the lymphangiogenesis and lymph node metastasis of breast cancer. Methods  The expressions of HIF-1α and VEGF-C were investigated by means of immunohistochemistry in samples from 78 cases of breast cancer and 20 cases of breast benign lesions. The density of the lymphatic microvessels immunohistochemically stained by D2-40 antibody was calculated. The relationships between HIF-1α, VEGF-C, LVD and clinicopathological parameters were analyzed statistically. Results  HIF-1α expression occurred in 52 out of the 78 tumor samples (66.67%), while VEGF-C expression was observed in 41 out of the 78 tumor samples (52.56%). HIF-1α and VEGF-C expressions in breast cancer were significantly higher than those in beingn disease (15% and 10%; χ2=17.26, P=0.000; χ2=11.71, P=0.001). The expressions of HIF-1α and VEGF-C were significantly correlated with regional lymph nodal involvement (χ2=5.80, P=0.016; χ2=7.26, P=0.007) as well as late TNM classification (χ2=8.51, P=0.004; χ2=6.02, P=0.014), disregarding the patient’s age, tumor diameter, histological grade and pathologic type (P＞0.05). In addition, HIF-1α expression was positively correlated with VEGF-C expression (r=0.254, P=0.025). Higher LVD was found in both high HIF-1α and high VEGF-C expression cases (t=2.19, P=0.017; t=3.25, P=0.001). Conclusion  HIF-1α may play a crucial role in the lymphangiogenesis and lymph node metastasis by regulating the expression of VEGF-C in breast cancer. Therefore, HIF-1α may become a particularly promising target for controlling lymph node metastasis in breast cancer.

Key words: Hypoxia inducible factor-1α, Vascular endothelial growth factor-C, Lymphangiogenesis, Breast neoplasms