Breast cancer is a heterogeneous disease with wide range of clinical behaviour. Tumour angiogenesis and metastasis have been considered as prognostic markers of the breast carcinoma, and c-Met, a transmembrane receptor tyrosine kinase has been implicated in both these processes of tumour progression. This study was conducted to elucidate c-Met and downstream signalling pathways in breast cancer and correlate with angiogenesis as assessed by microvessel density (MVD) and other prognostic parameters including lymph node metastases. Microvessel density (MVD) was assessed by endothelial cell (CD34) marker in breast cancers. c-Met was evaluated by immunohistochemistry for protein expression and by copy number assay for amplification at gene level. PCR array for gene expression related to c-Met, RAS-MAPK, PI3K-AKT and angiogenesis pathway was performed by real-time PCR. c-Met protein, copy number and mRNA expression did not differ significantly with the lymph node status or MVD. However, Her-2 overexpressing group showed c-Met protein overexpression and amplification. c-Met protein overexpression was also noted in the Luminal B subtype though no amplification was noted. Thus, the c-Met immunohistochemistry score and the c-MET copy numbers did not correlate with each other. c-Met downstream pathway genes (RAS-MAPK, PI3K-AKT and angiogenesis pathway) showed significant upregulation in Luminal B molecular subtype, lymph node-positive cases and cases with high MVD. The downstream signalling pathways (angiogenesis, RAS-MAPK and PI3K-AKT) were associated high MVD, lymph node metastases, and Her-2 and Luminal B subtype. Since inhibitors of these pathways are commercially available, these can be of therapeutic significance.

中文翻译：

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肿瘤血管生成和c-Met途径激活-对乳腺癌的影响。

乳腺癌是一种具有广泛临床行为的异质性疾病。肿瘤血管生成和转移已被认为是乳腺癌的预后标志物，而跨膜受体酪氨酸激酶c-Met参与了这两个肿瘤进展过程。进行这项研究以阐明乳腺癌中的c-Met和下游信号通路，并与微血管密度（MVD）和其他预后参数包括淋巴结转移评估的血管生成相关。通过血管内皮细胞（CD34）标记评估乳腺癌中的微血管密度（MVD）。通过免疫组织化学评估c-Met的蛋白质表达，并通过拷贝数分析评估基因水平的扩增。与c-Met，RAS-MAPK，PI3K-AKT和血管生成途径通过实时PCR进行。c-Met蛋白，拷贝数和mRNA表达与淋巴结状态或MVD无明显差异。但是，Her-2过表达组显示c-Met蛋白过表达和扩增。虽然未发现扩增，但在Luminal B亚型中也注意到c-Met蛋白的过表达。因此，c-Met免疫组化评分和c-MET拷贝数彼此不相关。c-Met下游通路基因（RAS-MAPK，PI3K-AKT和血管生成通路）在Luminal B分子亚型，淋巴结阳性病例和高MVD病例中显示出明显的上调。下游信号通路（血管生成，RAS-MAPK和PI3K-AKT）与高MVD，淋巴结转移以及Her-2和Luminal B亚型相关。