Li Yu-Jun, Wei Zhi-Min, Meng Yun-Xiao, Ji Xiang-Rui
Department of Pathology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, Shandong Province, China.
World J Gastroenterol. 2005 Apr 14;11(14):2117-23. doi: 10.3748/wjg.v11.i14.2117.
To investigate whether abnormal expression of beta-catenin in conjunction with overexpression of cyclinD1, c-myc and matrix metalloproteinase-7 (MMP-7) correlated with the carcinogenesis, metastasis and prognosis of pancreatic cancer, and to analyze the relationship of beta-catenin expression with cyclinD1, c-myc and MMP-7 expression.
Using immunohistochemistry, we examined the expression of beta-catenin, cyclinD1, c-myc and MMP-7 in 47 pancreatic adenocarcinoma tissues, 12 pancreatic intraepithelial neoplasia (PanIN) and 10 normal pancreases, respectively. Proliferation cell nuclear antigen was also tested as the index of proliferative activity of pancreatic cancer cells.
In 10 cases of normal pancreatic tissues, epithelial cells showed equally strong membranous expression of beta-catenin protein at the cell-cell boundaries, but the expression of cyclinD1, c-myc and MMP-7 was negative. The expression of beta-catenin, cyclinD1, c-myc and MMP-7 in PanIN and pancreatic adenocarcinoma tissues had no significant difference [6/12 and 32/47 (68.1%), 6/12 and 35/47 (74.5%), 5/12 and 33/47 (70.2%), 7/12 and 30/47 (63.8%), respectively]. The abnormal expression of beta-catenin was significantly correlated to metastasis and one-year survival rate of pancreatic cancer, but had no relation with size, differentiation and cell proliferation. The expression of cyclinD1 was correlated with cell proliferation and extent of differentiation, but not with size, metastasis and one-year survival rate of the pancreatic cancer. The expression of c-myc was not correlated with size, extent of differentiation, metastasis and 1-year survival rate, but closely with cell proliferation of pancreatic cancer. The overexpression of MMP-7 was significantly associated with metastasis and 1-year survival rate of pancreatic cancer, but not with size, extent of differentiation and cell proliferation. There was a highly significant positive association between abnormal expression of beta-catenin and overexpression of cyclinD1, c-myc and MMP-7 not only in PanIN (r = 1.000, 0.845, 0.845), but also in pancreatic cancer (r = 0.437, 0.452, 0.435).
The abnormal expression of beta-catenin plays a key role in the carcinogenesis and progression of human pancreatic carcinoma by up-regulating the expression of cyclinD1, c-myc and MMP-7, resulting in the degradation of extracellular matrix and uncontrolled cell proliferation and differentiation. beta-catenin abnormal expression and MMP-7 overexpression may be considered as two useful markers for determining metastasis and prognosis of human pancreatic cancer.
探讨β-连环蛋白异常表达联合细胞周期蛋白D1、c-myc和基质金属蛋白酶-7（MMP-7）过表达与胰腺癌的发生、转移及预后是否相关，并分析β-连环蛋白表达与细胞周期蛋白D1、c-myc和MMP-7表达的关系。
采用免疫组织化学方法，分别检测47例胰腺腺癌组织、12例胰腺上皮内瘤变（PanIN）和10例正常胰腺组织中β-连环蛋白、细胞周期蛋白D1、c-myc和MMP-7的表达。增殖细胞核抗原也作为胰腺癌细胞增殖活性指标进行检测。
10例正常胰腺组织中，上皮细胞在细胞间边界处β-连环蛋白蛋白呈同等强度的膜性表达，但细胞周期蛋白D1、c-myc和MMP-7表达为阴性。PanIN和胰腺腺癌组织中β-连环蛋白、细胞周期蛋白D1、c-myc和MMP-7的表达无显著差异[分别为6/12和32/47（68.1%）、6/12和35/47（74.5%）、5/12和33/47（70.2%）、7/12和30/47（63.8%）]。β-连环蛋白异常表达与胰腺癌转移及1年生存率显著相关，但与肿瘤大小、分化程度及细胞增殖无关。细胞周期蛋白D1表达与细胞增殖及分化程度相关，但与胰腺癌肿瘤大小、转移及1年生存率无关。c-myc表达与胰腺癌肿瘤大小、分化程度、转移及生存一年率无关，但与胰腺癌细胞增殖密切相关。MMP-7过表达与胰腺癌转移及1年生存率显著相关，但与肿瘤大小、分化程度及细胞增殖无关。β-连环蛋白异常表达与细胞周期蛋白D1、c-myc和MMP-7过表达不仅在PanIN中（r = 1.000、0.845、0.845），而且在胰腺癌中（r = 0.437、0.452、0.435）均呈高度显著正相关。
β-连环蛋白异常表达通过上调细胞周期蛋白D1、c-myc和MMP-7的表达，在人胰腺癌的发生和进展中起关键作用，导致细胞外基质降解及细胞增殖和分化失控。β-连环蛋白异常表达和MMP-7过表达可被视为判断人胰腺癌转移和预后的两个有用标志物。
