β-连环蛋白、细胞周期蛋白D1和c-myc表达与胰腺癌发生及生物学行为的关系

Relationship between the expression of β-cat, cyclin D1 and c-myc and the occurance and biological behavior of pancreatic cancer

目的 研究β-连环蛋白(β-cat)的异常表达、细胞周期蛋白D1(cyclin D1)和 c-myc的高表达与胰腺癌发生、增殖、浸润、转移和预后的关系。方法 应用免疫组织化学PicTure^(TM)二步法,检测47例胰腺癌组织、12例胰腺导管上皮内肿瘤(上皮中度不典型增生)和10例正常胰腺组织中β-cat、cyclin D1和c-myc的表达。同时检测胰腺癌增殖细胞核抗原(PCNA),作为胰腺癌增殖状态的指标。结果 β-cat在10例正常胰腺组织均呈正常表达,而cyclin D1和c-myc均呈阴性。三者在胰腺导管上皮内肿瘤和胰腺癌中的表达率差异无显著性[分别为6/12和68.1％(3/47)、6/12和74.5％(35/47)、5/12和70.2％(33/47),均P>0.05]。β-cat异常表达率与胰腺癌的转移和1年生存率显著相关(均P<0.05),而与胰腺癌大小、分化程度、增殖活性及浸润无关(均P>0.05)。cyclin D1的表达率与胰腺癌的增殖和分化程度有关(均P<O.05),与胰腺癌大小、浸润、转移和1年生存率无关(均P>0.05)。c-myc的表达率与胰腺癌的大小、分化程度、浸润、转移和1年生存率无关(均P>0.05),而与胰腺癌组织的增殖活性密切有关(P<0.05)。β-cat异常表达与cyclin D1和c-myc的高表达在胰腺导管上皮内肿瘤和胰腺癌中均有显著的正相关性(均P<0.05,r=1.000、0.845、0.437、0.452)。结论

Objective To study the relationship between the abnormal expression of β-catenin (β-cat) and the high expressions of cyclin D1 and c-myc and the occurance, proliferation, infiltration, metastasis and prognosis of pancreatic cancer, and to provide rational basis for the clinical diagosis and treatment. Methods Immunohistochemical PicTure?was used to examine the expressions of β-cat, cyclin D1 and c-myc in 47 cases of the cancerous tissue of pancreas, 12 cases of the pancreatic intraepithelial neoplasia and 10 cases of normal tissue of pancreas, respectively. Pancreatic cancer proliferation cell nuclear antigen (PCNA) was also tested as the index of the extent of proliferation of the pancreatic cancer. Results β-cat was expressed normally in the 10 cases of the normal pancreatic tissue, while cyclin D1 and c-myc were negative. The expression rates of β-cat, cyclin D1 and c-myc in the tissues of the pancreatic intraepithelial neoplasia and the pancreatic cancer had no significant difference [6/12 and 68. 1% (32/47) , 6/12和74.5% (35/47),5/12 and 70.2% (33/47) respectively;P values were all more than 0.05]. The abnormal expression rate of β-cat was significantly correlated to the metastasis of the pancreatic cancer and the one-year survival rate ( both P < 0. 05) , but had no relation with the size, the extent of differentiation, the activity of proliferation, or infiltration of the pancreatic cancer ( both P > 0. 05 ) . The expression rate of cyclin D1 was correlated with the proliferation of the pancreatic cancer and the extent of differentiation ( both P < 0. 05 ) , but not with the size, infiltration , metastasis, or one-year survival rate of the pancreatic cancer (both P >0. 05). The expression rate of c-myc was not correlated with the size, the extent of proliferation, infiltration , metastasis, or one-year survival rate ( both P > 0. 05) , but closely with the proliferation activity of the cancerous tissue of pancreas ( P < 0. 05). The abnormal expression of β-cat and the high expressions of cyclin D1 and c-myc had a parallel relationship with the pancreatic intraepithelial neoplasia and pancreatic cancer ( both P < 0. 05 , γ= 1. 000,0. 845 ,0. 437,0. 452). Conclusions The abnormal expression of β-cat activates cyclin D1 and c-myc, and results in the unchecked proliferation and differentiation, which may play an important role in the genesis of the pancreatic cancer. The abnormal expression of β-cat is one of the mechanisms for the spread of pancreatic cancer and an index in the molecular biology to determine the metastasis and prognosis of pancreatic cnacer.