Z Gastroenterol 2012; 50 - K294
DOI: 10.1055/s-0032-1324229

Epithelial-mesenchymal transition in ampullary cancer

UF Wellner 1, NR Simanjuntak 1, D Bausch 1, I Kohler 2, T Brabletz 1, T Keck 1
  • 1Universität Freiburg, Allgemein- und Viszeralchirurgie, Freiburg, Germany
  • 2Universität Freiburg, Pathologisches Institut, Freiburg, Germany

Aims: Ampullary cancer is a relatively rare disease and can frequently be treated by surgical resection. There are two main subtypes, intestinal and pancreatobiliary. ZEB1 is a regulator of epithelial-mesenchymal transition (EMT).

Materials and methods: We studied the occurrence and mechanisms of EMT in ampullary carcinoma using immuno-histochemical analysis from human tissue samples and two established human ampullary carcinoma cell lines.

Results: Immunohistochemical (IHC) analysis of human ampullary cancer tissue showed lymph node metastasis to be associated with tumor budding and loss of CDX2 expression, associated with the pancreatobiliary phenotype. Overall, the degree of EMT was only moderate as Vimentin or ZEB1 expressions were almost never observed in tumor tissue. The two ampullary cancer cell lines displayed a strong EMT phenotype, evidenced by spindle form cell shape, diffuse colony growth pattern, high ZEB1 and Vimentin expression, low levels of E-Cadherin and micro-RNA 200c and strong matrigel transmigration. The intestinal subtype marker CK20 was expressed in all cell lines including pancreatic cancer cell lines, but CDX2 expression was only found at very low levels. Upon knockdown of ZEB1 in vitro, E-Cadherin expression was increased, whereas Vimentin expression, spindle shape and diffuse colony growth pattern, matrigel transmigration as well as tumor sphere formation decreased. The expression of tumor subtype markers did not change with transient ZEB1 knockdown. Treatment with TGF-ß did not further increase the high ZEB1 levels but induced a slight further decrease in E-Cadherin expression and increase of diffuse growth pattern.

Conclusion: Invasion and metastasis of ampullary cancer are associated with EMT. The pancreatobiliary type of ampullary cancer displays more signs of EMT than the intestinal type. High ZEB1 expression levels could not be found in human tumor tissue, but in vitro experiments show that EMT in ampullary cancer cell lines is regulated by ZEB1.