Jan Yi-Yin, Yeh Ta-Sen, Yeh Jun-Nan, Yang Horng-Ren, Chen Miin-Fu
Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan.
Ann Surg. 2004 Jul;240(1):89-94. doi: 10.1097/01.sla.0000129492.95311.f2.
We sought to determine the expression of molecular markers in an animal model of cholangiocarcinoma compared with those in human cholangiocarcinoma.
Cholangiocarcinoma is a rare disease characterized by early intrahepatic and extrahepatic spread, which seriously limits the efficacy of surgery. Establishing an experimental model to study the cholangiocarcinogenesis is desirable.
Sprague-Dawley rats weighing 300 +/- 50 g were used for the study group. The animals were given 0.3% thioacetamide in tap water continuously. Thirty mass-forming peripheral cholangiocarcinoma patients also were studied. Expression of epidermal growth factor receptor (EGFR), MUC1, MUC2, MUC5AC, MMP-2, MMP-9, and p53 in both human and experimental rat cholangiocarcinoma was examined using immunohistochemistry.
Using thioacetamide 0.3% as a hepatoxin to induce cholangiocarcinoma in rats, microfoci of cancerous cells were detected from 12 weeks, and all experimental rats displayed diffuse mass-forming cholangiocarcinoma after 24 weeks. EGFR was strongly expressed in 14 (47%) of 30 human cholangiocarcinoms and 24 (100%) of 24 rat cholangiocarcinomas, respectively. MUC1 was strongly expressed in all human and rat cholangiocarcinomas, whereas MUC2 and MUC5AC were focally and weakly expressed. MMP-2 and MMP-9 were strongly expressed in 22 (73%) of 30 human cholangiocarcinomas and 24 (100%) of 24 rat cholangiocarcinomas, respectively. p53 overexpression was detected in 9 (30%) of 30 human cholangiocarcinoma and none of the rat cholangiocarcinoma, respectively.
The expression of EGFR, apomucins, MMPs, and p53 in rat cholangiocarcinoma was strongly homologous to human cholangiocarcinoma. Thioacetamide-induced cholangiocarcinoma in rats provides an excellent model for investigating cholangiocarcinogenesis in vivo.
我们试图确定胆管癌动物模型中分子标志物的表达，并与人类胆管癌中的表达进行比较。
胆管癌是一种罕见疾病，其特征为早期肝内和肝外扩散，这严重限制了手术疗效。建立一个实验模型来研究胆管癌发生过程是很有必要的。
体重300±50 g的Sprague-Dawley大鼠用于研究组。动物连续饮用含0.3%硫代乙酰胺的自来水。还对30例形成肿块的周围型胆管癌患者进行了研究。采用免疫组织化学法检测人及实验大鼠胆管癌中表皮生长因子受体（EGFR）、MUC1、MUC2、MUC5AC、基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）和p53的表达。
以0.3%硫代乙酰胺作为肝毒素诱导大鼠胆管癌，12周时检测到癌细胞微灶，24周后所有实验大鼠均表现为弥漫性肿块形成型胆管癌。EGFR在30例人类胆管癌中的14例（47%）和24例大鼠胆管癌中的24例（100%）中均有强表达。MUC1在所有人类和大鼠胆管癌中均有强表达，而MUC2和MUC5AC呈局灶性弱表达。MMP-2和MMP-9分别在30例人类胆管癌的22例（73%）和24例大鼠胆管癌的24例（100%）中强表达。p53过表达分别在30例人类胆管癌的9例（30%）中检测到，而在大鼠胆管癌中未检测到。
大鼠胆管癌中EGFR、黏蛋白、基质金属蛋白酶和p53的表达与人类胆管癌高度同源。硫代乙酰胺诱导的大鼠胆管癌为体内研究胆管癌发生提供了一个良好的模型。
