SSAT - Detailed Analysis of EMT and Tumor Budding Identifies Predictors of Long Term Survival in Pancreatic Ductal Adenocarcinoma

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Detailed Analysis of EMT and Tumor Budding Identifies Predictors of Long Term Survival in Pancreatic Ductal Adenocarcinoma
Peter Bronsert^*², Ilona Kohler², Dirk Bausch², Tobias Keck¹, Martin Werner², Sylvia Timme², Ulrich F. Wellner¹
¹Clinic for Surgery, UKSH Campus Lübeck, Lübeck, Germany; ²Institute of Pathology, University Medical Center, Freiburg, Germany

Background and Aim: Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive biology and poor prognosis even after resection. Long term survival is very rare and cannot be reliably predicted. Experimental data suggest an important role of epithelial-mesenchymal transition (EMT) in invasion and metastasis of PDAC. Tumor budding is regarded as the morphologic correlate of local invasion and cancer cell dissemination. The aim of this study was to evaluate the biologic and prognostic implications of EMT and tumor budding in PDAC of the pancreatic head.
Methods: Patients were identified from a prospectively maintained database and baseline, operative, histopathologic and follow-up data extracted. Serial tissue slices stained for Pan-Cytokeratin (PCK) served for analysis of tumor budding, and E-Cadherin (ECad), Beta-Catenin (BCat) and Vimentin (VIM) staining for analysis of EMT. Baseline, operative, standard pathology and immunohistochemical parameters were evaluated for prediction of long term survival (>= 30 months) in uni- and multivariate analysis.
Results: Intra- and intertumoral patterns of EMT marker expression and tumor budding provide evidence of partial EMT induction at the tumor-host interface. Lymph node ratio (LNR) and E-Cadherin expression in tumor buds were independent predictors of long term survival in multivariate analysis.
Conclusions: Detailed immunohistochemic assessment confirms a relationship between EMT and tumor budding at the tumor-host interface. A small group of patients with favorable prognosis can be identified by combined assessment of LNR and EMT in tumor buds.

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