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Prognostic Significance of ZEB1 Expression in Cancer Cells and Cancer Associated Fibroblasts in Pancreatic Head Cancer
Peter Bronsert*2, Ilona Kohler2, Dirk Bausch1, Martin Werner2, Tobias Keck1, Ulrich F. Wellner1
1Clinic for Surgery, UKSH Campus Lübeck, Lübeck, Germany; 2Institute of Pathology, University Medical Center, Freiburg, Germany
Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an aggressive biology and poor prognosis. Experimental evidence has suggested a role for the transcriptional repressor ZEB1 in epithelial-mesenchymal transition, invasion and metastasis in PDAC. ZEB1 expression has been observed in cancer cells as well as stromal fibroblasts. Our study aimed to evaluate the prognostic value of ZEB1 expression in PDAC tissue.
Methods: Patient baseline and follow-up data was extracted from a prospectively maintained database. After clinicopathological re-review, serial sliced tissue slides were immunostained for ZEB1 and Pan-Cytokeratin. ZEB1 expression in cancer cells and adjacent stromal fibroblasts was graded separately and correlated to routine histopathological parameters and survival after resection.
Results: N=117 cases of PDAC were included in the study. High ZEB1 expression in cancer cells and in stromal cancer associated fibroblasts (CAF) was significantly associated with poor prognosis. There was also a trend for poor prognosis with a lymph node ratio of over 0.10. In multivariate analysis, stromal ZEB1 expression grade was the only independent factor of survival after resection.
Conclusions: Our data suggest that ZEB1 expression in cancer cells as well as in stromal fibroblasts are strong prognostic factors in PDAC. Stromal ZEB1 expression is identified for the first time as an independent predictor of survival after resection of PDAC. This observation suggests that therapies targeting ZEB1 and its downstream pathways could hit both cancer cells and supporting CAF.
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