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. 2004 Jul;240(1):89-94.
doi: 10.1097/01.sla.0000129492.95311.f2.

Expression of epidermal growth factor receptor, apomucins, matrix metalloproteinases, and p53 in rat and human cholangiocarcinoma: appraisal of an animal model of cholangiocarcinoma

Yi-Yin Jan  1 , Ta-Sen Yeh, Jun-Nan Yeh, Horng-Ren Yang, Miin-Fu Chen
Affiliations

Expression of epidermal growth factor receptor, apomucins, matrix metalloproteinases, and p53 in rat and human cholangiocarcinoma: appraisal of an animal model of cholangiocarcinoma

Yi-Yin Jan et al. Ann Surg. 2004 Jul.

Abstract

Objective: We sought to determine the expression of molecular markers in an animal model of cholangiocarcinoma compared with those in human cholangiocarcinoma.

Summary background data: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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Figures

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FIGURE 1. Multiple mass-forming peripheral cholangiocarcinoma in Sprague-Dawley rat induced by thioacetamide 0.3% at 16 weeks.
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FIGURE 2. Strong expression of epidermal growth factor receptor in rat (A) and human (B) cholangiocarcinoma, respectively (original magnification, 400×).
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FIGURE 3. Strong expression of MUC1 in rat (A) and human (B) cholangiocarcinoma, respectively. Focal and weak expression of MUC2 in rat (C) and human (D) cholangiocarcinoma, respectively. Focal and weak expression of MUC5AC in rat (E) and human (F) cholangiocarcinoma, respectively (original magnification, 400×).
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FIGURE 4. Strong expression of MMP-2 in rat (A) and human (B) cholangiocarcinoma, respectively. Strong expression of MMP-9 in rat (C) and human (D) cholangiocarcinoma, respectively (original magnification, 400×).
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FIGURE 5. Negative p53 overexpression in rat cholangiocarcinoma (A); and strong p53 overexpression in human adenosquamous cholangiocarcinoma (B) (original magnification, 400×).
See this image and copyright information in PMC

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