Increased angiogenesis and lymphangiogenesis in inflammatory versus noninflammatory breast cancer by real-time reverse transcriptase-PCR gene expression quantification
Increased angiogenesis and lymphangiogenesis in inflammatory versus noninflammatory breast cancer by real-time reverse transcriptase-PCR gene expression quantification
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DOI：
10.1158/1078-0432.ccr-04-0063
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发表时间：
2004-12-01
影响因子：
11.5
通讯作者：
Dirix, LY
中科院分区：
文献类型：
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作者：
Van der Auwera, I;Van Laere, SJ;Dirix, LY
目的：炎性乳腺癌是局部晚期乳腺癌的一种独特的侵袭性形式，具有独特的临床和病理特征。最近，在炎性乳腺癌标本中发现了强烈的血管生成的组织学证据。本研究的目的是确认炎性乳腺癌的血管生成表型，并探讨其诱导淋巴管生成的潜力。实验设计：采用实时定量逆转录酶-PCR检测肿瘤血管生成和淋巴管生成相关因子[血管内皮生长因子（VEGF）-A，VEGF-C，VEGF-D，Flt-1，KDR，Flt-4]的mRNA水平。Ang-1、Ang-2、Tie-1、Tie-2、环氧合酶-2、成纤维细胞生长因子-2（FGF-2）、Egr-1、Prox-1和LYVE-1]。应用组织芯片技术和免疫组化技术研究炎性乳腺癌和非炎性乳腺癌中某些血管生成因子的差异蛋白表达。活性淋巴管生成进一步评估通过测量淋巴管内皮细胞proliferation.Results：炎性乳腺癌标本有显着高于非炎性乳腺癌标本的以下基因的mRNA表达水平：KDR（P 0.033），Ang-1，（P = 0.0001），Tie-1（P = 0.001）、Tie-2（P 0.001）、FGF-2（P = 0.002）、VEGF-C（P 0.001）、VEGF-D（P = 0.012）、Flt-4（P = 0.001）、Prox-1（P 0.005）和LYVE-1（P = 0.013）。FGF-2和环氧合酶-2的高mRNA水平对应于通过免疫组织化学增加的蛋白表达。炎性乳腺癌标本中增殖淋巴管内皮细胞的比例显着高于非炎性乳腺癌标本（P = 0.033）。结论：使用实时定量逆转录酶-PCR和免疫组化，我们证实了强烈的血管生成活性在炎性乳腺癌，并证明存在活跃的淋巴管生成在炎性乳腺癌。这可能有助于解释炎性乳腺癌通过淋巴和血行途径的高转移潜力。这两种途径都是治疗炎性乳腺癌的潜在靶点。
Purpose: Inflammatory breast cancer is a distinct and aggressive form of locally advanced breast cancer with unique clinical and pathological features. Recently, histologic evidence of intense angiogenesis was found in inflammatory breast cancer specimens. The aim of this study was to confirm the angiogenic phenotype of inflammatory breast cancer and to investigate its potential to induce lymphangiogenesis.Experimental Design: Real-time quantitative reverse transcriptase-PCR was used to measure levels of mRNA of tumor angiogenesis and lymphangiogenesis-related factors [vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF-D, FIt-1, KDR, Flt-4. Ang-1, Ang-2, Tie-1, Tie-2, cyclooxygenase-2, fibroblast growth factor-2 (FGF-2), Egr-1, Prox-1, and LYVE-1] in tumor specimens of 16 inflammatory breast cancer and 20 noninflammatory breast cancer patients. Tissue microarray technology and immunohistochemistry were used to study differential protein expression of some of the angiogenic factors in inflammatory breast cancer and noninflammatory breast cancer. Active lymphangiogenesis was further assessed by measuring lymphatic endothelial cell proliferation.Results: Inflammatory breast cancer specimens had significantly higher mRNA expression levels than noninflammatory breast cancer specimens of the following genes: KDR (P 0.033), Ang-1, (P = 0.0001), Tie-1 (P = 0.001), Tie-2 (P 0.001), FGF-2 (P = 0.002), VEGF-C (P 0.001), VEGF-D (P = 0.012), Flt-4 (P = 0.001), Prox-l (P 0.005), and LYVE-1 (P = 0.013). High mRNA levels of FGF-2 and cyclooxygenase-2 corresponded to increased protein expression by inummohistochemistry. Inflammatory breast cancer specimens contained significantly higher fractions of proliferating lymphatic endothelial cells than noninflammatory breast cancer specimens (P = 0.033).Conclusions: Using real-time quantitative reverse transcriptase-PCR and immunohistochemistry, we confirmed the intense angiogenic activity in inflammatory breast cancer and demonstrated the presence of active lymphangiogenesis in inflammatory breast cancer. This may help explain the high metastatic potential of inflammatory breast cancer by lymphatic and hematogenous route. Both pathways are potential targets for the treatment of inflammatory breast cancer.