Nakopoulou L, Gakiopoulou H, Keramopoulos A, Giannopoulou I, Athanassiadou P, Mavrommatis J, Davaris P S
Departments of Pathology, Gynaecology and Obstetrics, Medical School, University of Athens, Greece.
Histopathology. 2000 Apr;36(4):313-25. doi: 10.1046/j.1365-2559.2000.00847.x.
Receptor-type tyrosine kinases are important in cell signal transduction and proliferation. Abnormal expression of tyrosine kinases often leads to malignant transformation. c-met is a tyrosine kinase receptor and its ligand is hepatocyte growth factor (HGF). In this study, we have evaluated c-met expression in 69 invasive breast carcinomas and statistically analysed this expression with known clinicopathological prognostic parameters and patients' survival. We also studied for the first time c-met expression in association with E-cadherin and beta-catenin expression.
Immunohistochemistry (ABC-HRP method) was peformed for the detection of c-met, E-cadherin and beta-catenin. c-met immunoreactivity was observed in 58% of cases and was associated with the lobular type of breast carcinomas (P = 0.012), low histological grade ductal carcinomas (P = 0.05), favourable prognostic and predictive factors such as oestrogen and progesterone receptor immunohistochemical expression and negative c-erbB-2 expression (P = 0.05, P = 0.014 and P = 0.03, respectively). c-met immunoreactivity did not correlate with lymph node status, tumour size and stage of the disease. Cox's proportional hazard regression model demonstrated that tumours with positive c-met immunoreactivity correlated significantly with favourable patients' survival (P = 0.028). When c-met staining was compared with E-cadherin and beta-catenin expression, a statistical significant correlation was established between c-met immunoreactivity and abnormal beta-catenin expression (P = 0.025) suggesting possible involvement of c-met in the downregulation of the E-cadherin-catenin complex, possibly through tyrosine phosphorylation of beta-catenin.
c-met immunohistochemical expression seems to be associated with abnormal beta-catenin expression, good prognostic and predictive factors and favourable outcome in breast cancer patients.
受体型酪氨酸激酶在细胞信号转导和增殖中起重要作用。酪氨酸激酶的异常表达常导致恶性转化。c-met是一种酪氨酸激酶受体，其配体是肝细胞生长因子（HGF）。在本研究中，我们评估了69例浸润性乳腺癌中c-met的表达，并将该表达与已知的临床病理预后参数及患者生存率进行了统计学分析。我们还首次研究了c-met表达与E-钙黏蛋白和β-连环蛋白表达的关系。
采用免疫组织化学（ABC-HRP法）检测c-met、E-钙黏蛋白和β-连环蛋白。在58%的病例中观察到c-met免疫反应性，其与小叶型乳腺癌相关（P = 0.012）、低组织学分级导管癌相关（P = 0.05），与雌激素和孕激素受体免疫组化表达及c-erbB-2阴性表达等良好的预后和预测因素相关（分别为P = 0.05、P = 0.014和P = 0.03）。c-met免疫反应性与淋巴结状态、肿瘤大小和疾病分期无关。Cox比例风险回归模型显示，c-met免疫反应性阳性的肿瘤与患者良好的生存率显著相关（P = 0.028）。当比较c-met染色与E-钙黏蛋白和β-连环蛋白表达时，c-met免疫反应性与异常β-连环蛋白表达之间建立了统计学显著相关性（P = 0.025），提示c-met可能通过β-连环蛋白的酪氨酸磷酸化参与E-钙黏蛋白-连环蛋白复合物的下调。
c-met免疫组化表达似乎与异常β-连环蛋白表达、良好的预后和预测因素以及乳腺癌患者的良好结局相关。
