E-钙黏蛋白/β-连环蛋白复合物及细胞周期蛋白D1在乳腺癌中的意义
Significance of E-cadherin/beta-catenin complex and cyclin D1 in breast cancer.
作者信息
Lim Sung-Chul, Lee Mi-Sook
机构信息
Department of Pathology, College of Medicine, Chosun University Hospital, Dong-ku, Kwangju, Korea.
出版信息
Oncol Rep. 2002 Sep-Oct;9(5):915-28.
E-cadherin and beta-catenin are important epithelial adhesion molecules in normal epithelium. Loss of E-cadherin - beta-catenin adhesion is an important step in the progression of many epithelial malignancies. beta-catenin plays also a role in intracellular signaling and can function as an oncogene when binds to the T-cell factor 4 (Tcf4)-binding site in the promotor region of cyclin D1 and transactivates genes after translocation to the nucleus. We evaluated the immunohistochemical expression pattern of E-cadherin, beta-catenin in relationship with cyclin D1 overexpression, tumor stage, clinicopathologic parameters and patient survival in 128 mammary infiltrating duct carcinomas. The expression of E-cadherin/beta-catenin complex and beta-catenin/cyclin D1 double staining with confocal scanning laser microscope was evaluated. There were aberrant expressions in 78% of E-cadherin, 79% of beta-catenin, and 66% of cyclin D1 in breast cancer. There was correlation of aberrant expression of E-cadherin or beta-catenin with lymph node metastasis, survival rate, and survival length. However, there was no correlation of cyclin D1 overexpression with aberrant expression of E-cadherin or beta-catenin. No death was found in normal expression of beta-catenin, however lowest survival (50%) was found in nuclear beta-catenin expression. There was correlation of overexpression of cyclin D1 with survival rate and survival length. The highest survival rate and survival length were found in membranous normal beta-catenin expression group, however significant decrement of survival length was found in the groups of aberrant expression one or both of E-cadherin or/and beta-catenin. These results suggest that aberrant expression of E-cadherin, beta-catenin, and cyclin D1 may be involved in tumor metastasis, and analysis of the degree or the pattern of E-cadherin, beta-catenin, cyclin D1, and E-cadherin/beta-catenin complex may be good prognostic markers of mammary infiltrating duct carcinoma.
E-钙黏蛋白和β-连环蛋白是正常上皮组织中重要的上皮黏附分子。E-钙黏蛋白-β-连环蛋白黏附功能的丧失是许多上皮恶性肿瘤进展中的重要一步。β-连环蛋白在细胞内信号传导中也发挥作用,当它与细胞周期蛋白D1启动子区域的T细胞因子4(Tcf4)结合位点结合并转位至细胞核后激活基因时,可发挥癌基因的功能。我们评估了128例乳腺浸润性导管癌中E-钙黏蛋白、β-连环蛋白的免疫组化表达模式及其与细胞周期蛋白D1过表达、肿瘤分期、临床病理参数和患者生存率的关系。采用共聚焦扫描激光显微镜评估E-钙黏蛋白/β-连环蛋白复合物的表达以及β-连环蛋白/细胞周期蛋白D1的双重染色。乳腺癌中E-钙黏蛋白异常表达率为78%,β-连环蛋白为79%,细胞周期蛋白D1为66%。E-钙黏蛋白或β-连环蛋白的异常表达与淋巴结转移、生存率和生存时长相关。然而,细胞周期蛋白D1过表达与E-钙黏蛋白或β-连环蛋白的异常表达无关。β-连环蛋白正常表达时未发现死亡病例,而β-连环蛋白核表达时生存率最低(50%)。细胞周期蛋白D1过表达与生存率和生存时长相关。膜性β-连环蛋白正常表达组的生存率和生存时长最高,而E-钙黏蛋白或/和β-连环蛋白其中之一或两者异常表达组的生存时长显著缩短。这些结果表明,E-钙黏蛋白、β-连环蛋白和细胞周期蛋白D1的异常表达可能参与肿瘤转移,对E-钙黏蛋白、β-连环蛋白、细胞周期蛋白D1及E-钙黏蛋白/β-连环蛋白复合物的程度或模式进行分析可能是乳腺浸润性导管癌良好的预后标志物。