Lymphangiogenesis induced by VEGF-C and VEGF-D promotes metastasis and a poor outcome in breast carcinoma: a retrospective study of 61 cases

Lymphangiogenesis induced by VEGF-C and VEGF-D promotes metastasis and a poor outcome in breast carcinoma: a retrospective study of 61 cases
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DOI:
10.1007/s10585-008-9180-4
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发表时间:
2008-11-01
影响因子:
4
通讯作者:
Guo, Shanyu
Guo, Shanyu
中科院分区:
医学3区
文献类型:
--
作者:
Gu, Yan;Qi, Xiaoliang;Guo, Shanyu

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目的评价乳腺癌患者淋巴管生成情况,探讨其发生机制,探讨淋巴管生成与乳腺癌进展的关系。方法对61例有完整临床和病理资料的乳腺癌进行分析。应用抗泊多普宁单抗对所有标本进行免疫组织化学染色,检测淋巴管密度(LVD),探讨其临床病理和预后价值。采用逆转录聚合酶链式反应(RT-PCR)和免疫组织化学方法检测血管内皮生长因子-C(VEGF-C)和血管内皮生长因子-D(VEGF-D)的表达,探讨其临床病理和预后价值及其与淋巴管生成的关系。结果乳腺癌LVD(6.28+/-3.73)显著高于乳腺良性病变(0.50+/-1.27),P&lt;0.01,并与淋巴结转移和高TNM分期显著相关,P&lt;0.01。乳腺癌组织中血管内皮生长因子C和血管内皮生长因子D的表达水平也显著高于乳腺良性病变组织,P&lt;0.01。随着血管内皮生长因子C和血管内皮生长因子D的高表达,LVD显著增加(P<0.01)。VEGF-C和VEGF-D高表达的患者预后不良的可能性更大,P&lt;0.05。结论淋巴管生成与乳腺癌的淋巴结转移、高TNM和不良预后密切相关。LVD可作为乳腺癌淋巴结转移的预测指标和预后因素。血管内皮生长因子-C和血管内皮生长因子-D在淋巴管生成中起重要作用,使肿瘤更具侵袭性,导致预后不良。
Purpose To evaluate lymphangiogenesis in patients with breast carcinoma, explore the underlying mechanism, and study the relationship between lymphangiogenesis and progression of breast carcinoma. Methods Sixty-one cases of breast carcinoma with complete clinical and pathological data were analyzed. Using an anti-podoplanin monoclonal antibody, an immunohistochemical study was made of all specimens to detect lymphatic vessel density (LVD) and to investigate its clinicopathological and prognostic value. VEGF-C and VEGF-D were observed by RT-PCR and immunostaining to investigate their clinicopathological and prognostic values and their relationship with lymphangiogenesis. Results LVD in breast carcinoma (6.28 +/- 3.73) was significantly higher than in benign mammary lesions (0.50 +/- 1.27), P < 0.01 and was significantly associated with lymphatic metastasis and high TNM stage, P < 0.01. The level of VEGF-C and VEGF-D expression was also significantly higher in breast carcinomas than in benign mammary lesions, P < 0.01. LVD increased significantly with higher expression of VEGF-C and VEGF-D, P < 0.01. Patients with high expression of VEGF-C and VEGF-D were observed to be more likely to have a bad outcome, P < 0.05. Conclusions Lymphangiogenesis was significantly associated with lymph node metastasis, high TNM, and poor outcome in breast carcinoma. LVD may serve as a predictor of lymph node metastasis and a prognostic factor in breast carcinoma. VEGF-C and VEGF-D play an important role in lymphangiogenesis making the carcinoma more aggressive and leading to a poor prognosis.